Association of Fish Oil and Physical Activity on Mobility Disability in Older Adults.
This study aimed to examine whether long-term fish oil (FO) supplementation is associated with a lower risk of mobility disability and enhances benefits of physical activity (PA). A total of 1635 sedentary adults age 70 to 89 yr from the Lifestyle Interventions and Independence for Elders single-blinded randomized, multicenter clinical trial, which compared a structured PA program to a health education program. Primary outcome was incident major mobility disability (MMD), defined by loss of ability to walk 400 m, measured every 6 months for an average of 2.6 yr. Secondary outcomes included persistent mobility disability, Short Physical Performance Battery, 400-m walk speed, and grip strength. A third of participants reported using FO at baseline (456 (28%); mean age, 78.5 yr; 70.5% women). MMD was experienced by 131 participants (28.7%) in the FO group and 405 (34.4%) participants in the nonuser group. After adjusting for confounders, FO supplementation was associated with a lower risk (HR, 0.78; 95% confidence interval (CI), 0.64-0.96) of incident MMD. However, there was no interaction (P = 0.19) between FO supplementation and PA intervention for MMD. For the secondary outcome of persistent mobility disability, the intervention association differed by supplementation (P = 0.002) with PA intervention associations of (HR, 1.36; 95% CI, 0.83-2.23) for users and (HR, 0.61; 95% CI, 0.46-0.81) for nonusers. Changes in physical performance outcomes were not modified by baseline FO supplementation or combination with PA. FO supplementation was associated with a lower risk of MMD in low to moderate functioning older adults. However, supplementation did not enhance the benefit of PA on risk of mobility disability. These results are hypothesis generating and need to be confirmed in randomized trials.


Event-based fractional order control.
The present study provides a generalization of event-based control to the field of fractional calculus, combining the benefits brought by the two approaches into an industrial-suitable control strategy. During recent years, control applications based on fractional order differintegral operators have gained more popularity due to their proven superior performance when compared to classical, integer order, control strategies. However, the current industrial setting is not yet prepared to fully adapt to complex fractional order control implementations that require hefty computational resources; needing highly-efficient methods with minimum control effort. The solution to this particular problem lies in combining benefits of event-based control such as resource optimization and bandwidth allocation with the superior performance of fractional order control. Theoretical and implementation aspects are developed in order to provide a generalization of event-based control into the fractional calculus field. Different numerical examples validate the proposed methodology, providing a useful tool, especially for industrial applications where the event-based control is most needed. Several event-based fractional order implementation possibilities are explored, the final result being an event-based fractional order control methodology.


Cardiovascular magnetic resonance of mitral valve length in hypertrophic cardiomyopathy.
Previous data suggest that mitral valve leaflets are elongated in hypertrophic cardiomyopathy (HCM), and mitral valve leaflet elongation may constitute a primary phenotypic expression of HCM. Our objective was to measure the length of mitral valve leaflets by cardiovascular magnetic resonance (CMR) in subjects with HCM caused by a Finnish founder mutation in the myosin-binding protein C gene (MYBPC3-Q1061X), carriers of the same mutation without left ventricular hypertrophy, as well as in unselected consecutive patients with HCM, and respective controls. Anterior mitral valve leaflet (AML) and posterior mitral valve leaflet (PML) lengths were measured by CMR in 47 subjects with the Q1061X mutation in the gene encoding MYBPC3 and in 20 healthy relatives without the mutation. In addition, mitral valve leaflet lengths were measured by CMR in 80 consecutive non-genotyped patients with HCM in CMR and 71 age- and gender-matched healthy subjects. Of the subjects with the MYBPC-Q1016X mutation, 32 had left ventricular hypertrophy (LVH, LV maximal wall thickness ≥ 13 mm in CMR) and 15 had no hypertrophy. PML was longer in patients with the MYBPC3-Q1061X mutation and LVH than in controls of the MYBPC group (12.8 ± 2.8 vs 10.6 ± 1.9 mm, P = 0.013), but the difference between the groups was not statistically significant when PML was indexed for BSA (P = 0.066), or when PML length was adjusted for BSA, age, gender, LV mass and ejection fraction (P = 0.195). There was no significant difference in the PML length in mutation carriers without LVH and controls (11.1 ± 3.4 vs 10.6 ± 1.9, P = 0.52). We found no difference in AML lengths between the MYBPC mutation carriers with or without hypertrophy and controls. In 80 consecutive non-genotyped patients with HCM, there was no difference either in AML or PML lengths in subjects with HCM compared to respective control subjects. In subjects with HCM caused by the Q1061X mutation in the MYBPC3 gene, the posterior mitral valve leaflets may be elongated, but mitral valve elongation does not constitute primary phenotypic expression of the disease. Instead, elongated mitral valve leaflets seem to be associated with body size and left ventricular remodeling.


Embryonal carcinoma metastasis from pure testicular teratoma mimicking a complex renal cyst.
Teratoma is frequently found in mixed germ cell testicular tumors in up to 80% of cases, but as a pure component it is reported in only 2-6% of cases. Metastatic disease may be seen in 29-76% of these cases in the adult population. We present the case of a 32 year old male patient diagnosed with a pure testicular teratoma in clinical stage I and a right renal cyst Bosniak IIF, as part of treatment he received chemotherapy, during which, radiological changes were observed at the level of renal cyst suggesting metastatic tumor.


Non-target ROIMCR LC-MS analysis of the disruptive effects of TBT over time on the lipidomics of Daphnia magna.
This study has investigated the temporal disruptive effects of tributyltin (TBT) on lipid homeostasis in Daphnia magna. To achieve this, the study used Liquid Chromatography-Mass Spectrometry (LC-MS) analysis to analyze biological samples of Daphnia magna treated with TBT over time. The resulting data sets were multivariate and three-way, and were modeled using bilinear and trilinear non-negative factor decomposition chemometric methods. These methods allowed for the identification of specific patterns in the data and provided insight into the effects of TBT on lipid homeostasis in Daphnia magna. Investigation of how are the changes in the lipid concentrations of Daphnia magna pools when they were exposed with TBT and over time using non-targeted LC-MS and advanced chemometric analysis. The simultaneous analysis of LC-MS data sets of Daphnia magna samples under different experimental conditions (TBT dose and time) were analyzed using the ROIMCR method, which allows the resolution of the elution and mass spectra profiles of a large number of endogenous lipids. Changes obtained in the peak areas of the elution profiles of these lipids caused by the dose of TBT treatment and the time after its exposure are analyzed by principal component analysis, multivariate curve resolution-alternative least square, two-way ANOVA and ANOVA-simultaneous component analysis. 87 lipids were identified. Some of these lipids are proposed as Daphnia magna lipidomic biomarkers of the effects produced by the two considered factors (time and dose) and by their interaction. A reproducible multiplicative effect between these two factors is confirmed and the optimal approach to model this dataset resulted to be the application of the trilinear factor decomposition model. The proposed non-targeted LC-MS lipidomics approach resulted to be a powerful tool to investigate the effects of the two factors on the Daphnia magna lipidome using chemometric methods based on bilinear and trilinear factor decomposition models, according to the type of interaction between the design factors.


Prevention of multiple pregnancies by restricting the number of transferred embryos: randomized control study.
The high incidence of multiple pregnancies is a major concern in the treatment of infertility by in vitro fertilization (IVF). Risks and costs are associated with multiple pregnancies and it is important to find a way to decrease multiple pregnancies. The standard protocol for IVF includes the transfer of two or three embryos. In this study, we compared the rate of single and multiple pregnancies between patients who received two and three embryos. One hundred and sixty-nine patients were randomly divided into two groups, with 106 cycles of IVF each. Group 1 received two embryos, and group 2 three. Group 1 had total 40 (37.8%) pregnancies, while group 2 had 29 (27.4%). The number of ongoing pregnancies was 33 (31.1%) in group 1 and 26 (24.5%) in group 2. The number of baby-take-home was 32 (30.1%) in group 1 and 26 (24.5%) in group 2. These results show that there was no significant difference between the two groups in both the total and ongoing pregnancies. On the other hand, the number of twin pregnancies was 6 (15.0%) in group 1 and 12 (41.4%) in group 2, showing a significant difference. Group 1 had no triplet pregnancies, while Group 2 had two. We conclude that the transfer of two embryos reduces the incidence of multiple pregnancies while maintaining an acceptable rate of pregnancy in IVF.


Raphe projections to the locus coeruleus in the rat.
Afferent projections to the locus coeruleus from the various raphe nuclei, particularly of the midbrain (nuclei raphe dorsalis and medianus) and pons (nuclei raphe pontis and magnus), have been studied in the rat by retrograde transport methods using horseradish peroxidase (HRP). The locus coeruleus, in both its dorsomedial and ventrolateral divisions, and in its various anterior-posterior components, were injected with 0.05 microliters of horseradish peroxidase following which various structures of the brainstem, particularly the raphe nuclei, were examined for HRP reactive cells. It was found that injections in most components of the locus coeruleus were associated with HRP positive cells in varying degrees of density in the nuclei raphe dorsalis, medianus, pontis, and magnus, with considerably sparser labelling in the anterior aspects of the medullary raphe nuclei pallidus and obscurus. Labelled cells were also seen in the nuclei of the solitary tract, contralateral locus coeruleus. lateral reticular areas of the pons and midbrain, nuclei pontis oralis and caudalis, vestibular nuclei, mesencephalic nucleus of the trigeminal nerve, fastigial nuclei of cerebellum and medial parabrachial nuclei. These data, showing widespread innervation of the locus coeruleus from all raphe nuclei, as well as many other brainstem areas, in the rat support the general view of heavy innervation of the locus coeruleus from both extra-raphe and raphe nulcei. These latter raphe projections, probably serotonergic in nature, provide anatomical support for the various experiments indicating considerable regulation of locus coeruleus activities, such as phasic events of REM sleep, among other, by widespread projections from most raphe nuclei was well as several other regions of the brainstem.


Can the implementation of the Opioid Start Talking form impact the amount of opioid use in patients after ankle fracture repair?
As part of 2018 legislation aimed at fighting the opioid epidemic, the Michigan Department of Health and Human Services (MDHHS) published the "Opioid Start Talking" (OST) Form on June 1, 2018. We examined if the implementation of the OST form led to an identifiable decrease in patient opioid use. Specifically, we examined the opioid prescription quantities in patients who sustained ankle fractures that required open reduction internal fixation (ORIF). Retrospective. Hospital medical records and Michigan Automated Prescription Database (MAPS) were analyzed for similar ankle fracture patients operated on by two surgeons prior to and after the initiation of the OST form. Records allowed us to track opioid filling through MAPS for 120 days after surgery in two groups: preimplementation (PRE) and post-implementation (POST) OST groups. The gathered data were analyzed by the investigators along with a staff statistician. Single-institution orthopedic practice. Seventy eight patients Main outcome measure: Average morphine milligram equivalent (MME) per patient encounter. Seventy eight patients were included in the final analysis after applying the exclusion criteria. There were 38 patients in the pre-OST form period and 40 in the post-OST form period groups. The pre-OST and post-OST groups were well matched between the two surgeons. There was no evidence of a statistically significant difference found in the median MME between patients from the pre-period group to the post-period group (median 59 vs 50, P = 0.61). In regard to the injury pattern, the bimalleolar MME median was 50 (38 = 25th percentile, 67 = 75th percentile; min-max 0-175) and the trimalleolar median MME was 63 (39 =25% percentile, 81 = 75th percentile; min-max 0-249) with a P value of 0.20. Overall, the administration of the OST form to patients with ankle fractures did not result in a decrease in MMEs prescribed within 120 days of surgery. Although it is a start in the battle against the opioid epidemic, further evaluation of the effectiveness of the OST form is necessary.


Carbon nanotube-encapsulated drug penetration through the cell membrane: an investigation based on steered molecular dynamics simulation.
Understanding the penetration mechanisms of carbon nanotube (CNTs)-encapsulated drugs through the phospholipid bilayer cell membrane is an important issue for the development of intracellular drug delivery systems. In the present work, steered molecular dynamics (SMD) simulation was used to explore the possibility of penetration of a polar drug, paclitaxel (PTX), encapsulated inside the CNT, through a dipalmitoylphosphatidylcholine bilayer membrane. The interactions between PTX and CNT and between PTX and the confined water molecules inside the CNT had a significant effect on the penetration process of PTX. The results reveal that the presence of a PTX molecule increases the magnitude of the pulling force. The effect of pulling velocity on the penetration mechanism was also investigated by a series of SMD simulations, and it is shown that the pulling velocity had a significant effect on pulling force and the interaction between lipid bilayer and drug molecule.


Medication-related problems commonly occurring in an Australian community setting.
This study characterised medication-related problems in 1000 Australian patients living in the community, and who were considered at risk of medication misadventure. A review was undertaken of 1000 clinical case notes, developed during the delivery of medication management reviews. Patient demographics, medications used, medical conditions and medication-related problems were categorised according to established classification systems. Descriptive analyses were undertaken. Overall, 2222 problems were identified. Ninety per cent of patients had at least one medication-related problem. One in three people were found to require additional monitoring, one in four required additional medication, one in four were using the wrong or inappropriate medication and one in five were using insufficient medication. Cardiovascular, nervous system, alimentary and respiratory medicines were most commonly implicated, accounting for 69% of the medication-related problems. This analysis reveals the need for ongoing vigilance of, and support for, people at high risk of medication misadventure. This information is also useful for informing the design of public health or health promotion strategies aiming to reduce the prevalence of these problems.


Measuring Autophagic Cargo Flux with Keima-Based Probes.
Autophagy and autophagy-associated genes are implicated in a growing list of cellular, physiological, and pathophysiological processes and conditions. Therefore, it is ever more important to be able to reliably monitor and quantify autophagic activity. Whereas autophagic markers, such as LC3 can provide general indications about autophagy, specific and accurate detection of autophagic activity requires assessment of autophagic cargo flux. Here, we provide protocols on how to monitor bulk and selective autophagy by the use of inducible expression of exogenous probes based on the fluorescent coral protein Keima. To exemplify and demonstrate the power of this system, we provide data obtained by analyses of cytosolic and mitochondrially targeted Keima probes in human retinal epithelial cells treated with the mTOR-inhibitor Torin1 or with the iron chelator deferiprone (DFP). Our data indicate that Torin1 induces autophagic flux of cytosol and mitochondria to a similar degree, that is, compatible with induction of bulk autophagy, whereas DFP induces a highly selective form of mitophagy that efficiently excludes cytosol.


Current trends in the structure-activity relationship studies of the endogenous agouti-related protein (AGRP) melanocortin receptor antagonist.
Agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin-3 and -4 (MC3R and MC4) G-protein coupled receptors. The 87-132 amino acid C-terminal domain of hAGRP possesses five disulfide bridges and a well-defined three-dimensional structure that displays full biological activity as compared to the full-length protein. Based on the NMR structure of the C-terminal AGRP(87-132), a novel mini-protein, referred to as "Mini-AGRP" was designed that exhibited receptor binding affinity and antagonism similar to that of the parent hAGRP(87-132) protein. It was demonstrated that this new-engineered protein autonomously folds to the inhibitor cystine knot (ICK) motif. As this AGRP is a novel mammalian protein involved in energy homeostasis and possibly other physiological functions remaining to be identified, structure-function studies are starting to emerge toward the understanding of how this unique protein putatively interacts with the melanocortin receptors with the objective of designing potential therapeutic agents for in vivo physiological studies. This article summarizes the progress to date of AGRP-based structure-activity relationships and putative ligand-receptor interactions.


Why Does C5 Palsy Occur After Prophylactic Bilateral C4-5 Foraminotomy in Open-Door Cervical Laminoplasty? A Risk Factor Analysis.
Retrospective study. To evaluate the efficacy of bilateral C4-5 foraminotomy in preventing occurrence of postoperative C5 palsy and to identify possible risk factors for its development. A total of 70 consecutive patients who underwent open-door laminoplasty with bilateral C4-5 foraminotomy were included. Clinical, radiographic, and operative data was reviewed. Development of postoperative C5 palsy was analyzed. A total of 54 males and 16 females were reviewed. Mean age was 56 years (range, 30-86 years). The primary pathology was spondylosis in 76% of cases and ossified posterior longitudinal ligament in 21%. Radiographic evidence of C4-5 foraminal stenosis was seen in 81% of the patients. The mean duration of preoperative symptoms was 7 ± 19 months. Four (5.7%) out of 70 patients developed C5 palsy after open-door laminoplasty with bilateral C4-5 foraminotomy. Multivariate analysis showed that a long duration of preoperative symptoms (>12 months) and the presence of preoperative C4-5 T2-MRI cord signal change were statistically significant risk factors for the development of C5 palsy even after bilateral C4-5 foraminotomy in open-door laminoplasty (P < .0001 and P = .036, respectively). Prophylactic bilateral C4-5 foraminotomies do not completely eliminate the occurrence of C5 palsy. Prolonged duration of symptoms and presence of preoperative T2-MRI cord signal change increase the risk for developing postoperative C5 palsy despite foraminotomy.


Long-term captopril treatment. Angiotensin II receptors and responses.
The purpose of this study was to elucidate the mechanism of the antihypertensive effect of the angiotensin I (Ang I) converting enzyme inhibitor captopril in spontaneously hypertensive rats (SHR). Drinking responses, peripheral vascular reactivity, and angiotensin II (Ang II) receptor binding in both the brain and vascular smooth muscle were examined in control and captopril-treated SHR. Pregnant and nursing dams were treated with oral captopril (100 mg/kg). After weaning, offspring were maintained on captopril (50 mg/kg). The average systolic pressures after 21 weeks of captopril treatment were 122 +/- 3 mm Hg (male) and 118 +/- 4 mm Hg (female) as compared with 169 +/- 4 mm Hg (male) and 162 +/- 2 mm Hg (female) in age-matched controls. Drinking responses to intracerebroventricular (10 ng) and subcutaneous (100 micrograms/kg) administration of Ang I and II were attenuated in captopril-treated SHR in comparison to control SHR. Ang II receptor binding in the hypothalamus, thalamus, and septum of captopril-treated SHR was also significantly reduced. In contrast to a depressed angiotensinergic system in the brain, peripheral vascular reactivity to Ang II, as determined in isolated, artificially perfused kidneys, was elevated. Threshold and ED50 values for Ang II were significantly lower in captopril-treated SHR than in controls. Ang II receptor binding in aortic smooth muscle cells prepared from captopril-treated SHR was also significantly greater than in cells from controls. Thus, lifetime treatment with captopril induced alterations in the renin angiotensin systems in the periphery and brain that were manifested by changes in receptor binding and responsiveness to Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)


Measurement of the effect of Amazon smoke on inhibition of cloud formation.
Urban air pollution and smoke from fires have been modeled to reduce cloud formation by absorbing sunlight, thereby cooling the surface and heating the atmosphere. Satellite data over the Amazon region during the biomass burning season showed that scattered cumulus cloud cover was reduced from 38%in clean conditions to 0%for heavy smoke (optical depth of 1.3). This response to the smoke radiative effect reverses the regional smoke instantaneous forcing of climate from -28 watts per square meter in cloud-free conditions to +8 watts per square meter once the reduction of cloud cover is accounted for.


Direct Observation of Charge Injection of Graphene in the Graphene/WSe2 Heterostructure by Optical-Pump Terahertz-Probe Spectroscopy.
Charge transfer across the interface and interlayer coupling in the graphene van der Waals heterostructure, which is constructed by graphene and semiconducting transition metal dichalcogenides (TMDCs), is critical for their electronic and optoelectronic applications. Photo-induced charge injection from TMDC to graphene has been studied in several heterostructure photodetectors. However, the response time significantly varies among different reports, ranging from microseconds to milliseconds. In this work, using a graphene/WSe2 heterostructure as an example, we directly observe the carrier density change in graphene by time-resolved optical-pump terahertz (THz)-probe spectroscopy and show the ultrafast picosecond photoresponse of graphene. In the absence of photoexcitation, THz time-domain spectroscopic measurements show that WSe2 can transfer holes to graphene and pull down the Fermi level of graphene. After excitation by the ultrafast laser pulse, the transient THz response shows a rapid (∼0.35 ps) increase in the graphene conductivity mainly due to the hole injection from WSe2 into graphene. Unlike previous reports on band bend as the guidance mechanism for charge transfer, our results show that the relevant mechanism is the band offset across the atomically sharp interface.


Centralization of dairy farming facilities for improved economics and environmental quality.
In Japan, most farm animal excreta has been stored directly on farmland. Runoff from this storage has often caused water pollution. Biogasification is anticipated as an important technology to manage excreta properly, but complex problems hinder its introduction. Economic aspects of management have been especially difficult for dairy farmers. For this study, structural problems regarding introduction of biogasification into dairy farming were identified. Subsequently, a desirable system of dairy farming including biogasification was suggested, and an evaluation model of the financial balance was constructed. A case study using current financial balances of several systems of dairy farming was evaluated using the constructed model and actual data. The systems were based on several policy alternatives including the suggested system mentioned above. Results show that a farmer can obtain sufficient income from a system featuring centralization of dairy housing and biogasification facilities and coordinated management by over six farmers.


Hepatocellular Carcinoma Detection Using Machine Learning Techniques.
Hepatocellular carcinoma (HCC) is a form of primary cancer appearing in the liver. In this work used the hepatocellular carcinoma dataset from the UCI machine learning repository and tested different techniques for feature selection and classification. The following algorithms were used: decision trees, random forests, SVMs, k-NN classifiers, AdaBoost, and gradient boost. The best results were obtained using gradient boost with 84% accuracy and 93% precision. Finally, we deployed the model to a web application as a decision support system for clinicians.


Beyond positivist ecology: toward an integrated ecological ethics.
A post-positivist understanding of ecological science and the call for an "ecological ethic" indicate the need for a radically new approach to evaluating environmental change. The positivist view of science cannot capture the essence of environmental sciences because the recent work of "reflexive" ecological modelers shows that this requires a reconceptualization of the way in which values and ecological models interact in scientific process. Reflexive modelers are ecological modelers who believe it is appropriate for ecologists to examine the motives for their choices in developing models; this self-reflexive approach opens the door to a new way of integrating values into public discourse and to a more comprehensive approach to evaluating ecological change. This reflexive building of ecological models is introduced through the transformative simile of Aldo Leopold, which shows that learning to "think like a mountain" involves a shift in both ecological modeling and in values and responsibility. An adequate, interdisciplinary approach to ecological valuation, requires a re-framing of the evaluation questions in entirely new ways, i.e., a review of the current status of interdisciplinary value theory with respect to ecological values reveals that neither of the widely accepted theories of environmental value-neither economic utilitarianism nor intrinsic value theory (environmental ethics)-provides a foundation for an ecologically sensitive evaluation process. Thus, a new, ecologically sensitive, and more comprehensive approach to evaluating ecological change would include an examination of the metaphors that motivate the models used to describe environmental change.


Tree species preferences of foraging insectivorous birds in a northern hardwoods forest.
Birds searching for insects in the canopy of a northern hardwoods forest depart significantly from random in their use of tree species, even when these trees are generally similar in life form. All 10 foliage-dwelling bird species in the Hubbard Brook forest showed preferences for Yellow Birch, most had an aversion to Beech and Sugar Maple, and a few had special preferences for conifers or White Ash. Birds that glean prey from leaves had stronger tree species preferences than those that often hover for their prey, and were more influenced by tree species differences in foliage structure. The less common bird species and those for which northern hardwoods are marginal habitat had the most pronounced tree-species preferences. Food densities which are higher on Yellow Birch and specific adaptations to foraging in trees with particular foliage structures are considered major factors responsible for the observed tree species preferences. The implications of these findings for bird community structure and for forest management practices are discussed.


Effects of increase modes of shear force on granule disruption in upflow anaerobic reactors.
Sludge washout is listed among the top practical problems of the high rate upflow anaerobic reactors. This study investigated quantitatively two sludge washout processes operated under different hydrodynamic shear increase modes with the intervals of 1 and 10 days respectively. The results reveal that the sludge washout accompanying with large-scale granule disruption could lead to performance failure with heavy sludge loss ratio of about 46.1% at sludge loss rate about 0.35 gVSS L(-1) d(-1) during the process with shear increase interval of 1 day, while the highest sludge loss rate was only 0.12 gVSS L(-1) d(-1) during the process with 10-day interval. The intensified shear conditions could weaken the granules through inhibiting the extracellular polymers production and bioactivity. As consequences, an outbreak of large-scale granule disruption would raise and then significantly accelerate the sludge washout. Since long interval could provide the granules the opportunity to recover from these negative effects to some extent, the shear increase strategy of long interval over 10 days is favorably recommended to operate full-scale reactors during the start-up and shock load periods. The pioneer use of the micro particle image velocimetry in this study offers the possibility to discover the real hydrodynamic conditions around granules at microscale for the first time and reveals that the shear force exerts directly on the granular surface as a mechanical disruption force and big granules undergo high disruption force. The granule disruption is a result of the competition between the granule and the ambient hydrodynamic shear conditions rather than a process with shear force as a sole dominant factor. These could facilitate the understanding of the complicated interactions between the hydrodynamics and reactor performance and favor then a better control of the full-scale reactors.


Age-related changes in the central nervous system in selected domestic mammals and primates.
Aging is a process which operates at many levels of physiological, genetic and molecular organization and leads inevitably to death. Brain macroscopic changes by MRI investigation during aging were observed in humans and dogs but chimpanzees did not display significant changes. This suggestion led to the statement that brain aging is different in various species. Although human brain changes, e.g. β-amyloid storage, neurofibrillary tangle formation, lipofuscin, are relatively well known, we are still looking for a suitable animal model to study the mechanisms of aging and neurodegenerative diseases. Therefore, this paper presents a comparative analysis of the changes described in the brains of senile dog, horse and gorilla. In addition we present the latest, non-invasive methods that can be applied in the diagnosis of old age in mammals. Our considerations have shown that the best animal model for further studies and observations on aging is the dog.


Levels of human Rotaviruses and Noroviruses GII in urban rivers running through the city mirror their infection prevalence in populations.
Enteric viruses exposed to water pose a huge threat to global public health and can lead to waterborne disease outbreaks. A sudden increase in enteric viruses in some water matrices also underpins the prevalence of corresponding waterborne diseases in communities over the same time period. However, few efforts have been focused on water matrices whose viral pollution may best reflect the clinical prevalence in communities. Here, a one-year surveillance of human enteric viruses including Enteroviruses (EnVs), Rotaviruses (HRVs), Astroviruses (AstVs), Noroviruses GII (HuNoVsGII) and Mastadenoviruses (HAdVs) in four representative water matrices: an urban river (UR) running through city, effluent from Wastewater Treatment Plant (EW), raw water for Urban Water Treatment Plant (RW), and tap water (TW) were performed by qPCR. The relationship between the virus detection frequency at each site and their prevalence in clinical PCR assay was further analyzed. We found that the detection frequencies of HRVs, HuNoVsGII, and AstVs in stools peaked in winter, while EnVs peaked in autumn. No EnVs occurred in EW, RW, or TW, but HuNoVsGII and AstVs occurred intensively in winter. For UR, all types of enteric viruses could be detected and the levels of acute gastroenteritis viruses (HRVs, HuNoVsGII, AstVs, and HAdVs) were highest in autumn or winter, whereas EnVs peaked in summer. In terms of correlation analyses, only HRVs and HuNoVsGII levels in UR showed a strong positive correlation with their prevalence in clinical stool samples. This study indicated that HRVs and HuNoVsGII levels in URs may mirror the local virus prevalence, thereby implying the possibility of revealing their local epidemiology by monitoring them in the URs.


Sequence of the nucleocapsid protein gene of Machupo virus: close relationship with another South American pathogenic arenavirus, Junín.
The sequence of the nucleocapsid (N) protein of Machupo virus (causative agent of Bolivian haemorrhagic fever) has been determined, and used to infer a phylogenetic relationship to other arenaviruses. The relationship of the virus to Junín and Tacaribe viruses, together with previous demonstrations of antigenic similarity and cross-protection by heterologous viruses, suggest that vaccines developed against Argentine haemorrhagic fever might also be effective against the Bolivian disease.


MicroRNA-130a-3p impedes the progression of papillary thyroid carcinoma through downregulation of KPNB1 by targeting PSME3.
Papillary thyroid carcinoma (PTC) is the main type of thyroid cancer (THCA). Despite the good prognosis, some PTC patients may deteriorate into more aggressive disease, leading to poor survival. Our study aimed to explore the role of microRNA (miR)-130a-3p in regulating PTC. After transfection with miR-130a-3p-mimic, OE-PSME3, or miR-130a-3p-mimic + OE-KPNB1 in PTC cells (TPC-1), CCK-8, Transwell, scratch, and flow cytometry experiments were performed to analyze TPC-1 cell proliferation, invasion, migration, and apoptosis. Western blotting was used to detect proliferation or invasion-related protein markers (PCNA, E-cadherin, and N-cadherin). The RNA22 database, dual-luciferase reporter assay, and RNA pull-down assay were applied for the prediction and verification of the binding site between miR-130a-3p and PSME3. Pan-cancer software identified a positive correlation between PSME3 and KPNB1 in THCA. Co-immunoprecipitation was utilized to verify the interaction of PSME3 with KPNB1. Nude mice were transplanted with TPC-1 cells overexpressing miR-130a-3p. The tumors were isolated for detection of the expression of miR-130a-3p, PSME3, KPNB1, Ki-67, and CD31. miR-130a-3p was lowly expressed in PTC cell lines. Upregulation of miR-130a-3p repressed the expression of PSME3 and KPNB1 and reduced the malignancy of TPC-1 cells in vitro, shown by inhibited cell proliferation, invasion, migration, and the expression of PCNA and N-cadherin. Also, overexpressed miR-130a-3p inhibited the growth of xenograft tumors in nude mice. miR-130a-3p bound to PSME3 which interacted with KPNB1. miR-130a-3p impedes the progression of PTC by downregulating PSME3/KPNB1.


Visual acuity of children treated with chemotherapy for optic pathway gliomas.
Chemotherapy is the most common primary treatment modality for pediatric optic pathway gliomas (OPGs). Due to the risk of severe visual impairment, visual acuity (VA) has become a clinical parameter of fundamental importance for children with OPGs. Despite this reality, most studies omit crucial information necessary for analysis of the effect of chemotherapy on VA in patients with cerebral gliomas. The principal goal of this study was to determine the immediate and long-term visual outcome of children treated first with chemotherapy for OPGs. Retrospective, non-comparative, case series of children with OPGs treated initially with chemotherapy. VA was measured prior to chemotherapy, directly following chemotherapy, as well as at last follow-up. Seven children (14 eyes) were positive for the neurofibromatosis type-1 (NF1) mutation and 10 children (20 eyes) were without the NF1 mutation (sporadic). Three deaths, all in the sporadic cohort, occurred as a result of their OPG. Median follow-up time of survivors was 10.54 ± 4.36 (SD) years. Both NF1 mutation positive and sporadic cohorts had deterioration in VA over time; however, deterioration was only statistically significant in the sporadic population. The percentage of eyes with vision weaker than 20/200 prior to chemotherapy, directly following chemotherapy and at last follow-up grew from 18% to 24% to 38%, respectively. In both NF1 mutant and sporadic OPGs, VA deteriorated directly following chemotherapy as well as at long-term follow-up. Despite chemotherapy, eyes with severe functional impairment gradually increased over time.


Implementation of a Traumatic Brain Injury Guideline at A Department of Defense Level 1 Trauma Center.
Traumatic brain injury (TBI) is one of the most prevalent diagnoses among trauma populations and places significant strain on valuable rural hospital resources. Limited studies show safety and efficacy of implementation of a Brain Injury Guideline (BIG) protocol at a Department of Defense (DoD) Level 1 trauma center. Data from patients diagnosed with traumatic brain injury during the study period were collected from our institutional trauma database. A retrospective review was performed on patients identified in the database to collect demographic and injury related data. All primary and secondary outcome data were analyzed using two-tailed Fischer's exact tests, Pearson Chi-square tests, and non-parametric Mann Whitney U tests. A total of 354 patients were included in the study, 189 pre-implementation and 165 post-implementation. Demographics, head injury severity, initial HCT findings, and BIG classification distributions were well-matched. There was a significant reduction in neurosurgical consultations (NSC) (98.4% pre- to 77.0% post-implementation, P<0.001) and ICU admissions (84.1% pre-, 74.5% post-implementation, P=0.025) following protocol implementation. There were no differences between groups in ICU LOS (P=0.239), incidence of worsening findings on RHCT (P=0.894), or in-hospital mortality (P=0.814). There was a slight reduction in hospital LOS from 4.0d pre-implementation to 3.0d post-implementation (P=0.043). Implementation of a BIG protocol at our Level 1 trauma center suggested at a relationship with fewer NSCs and ICU admissions. Management of mild and moderate TBI by acute care and trauma surgeons without direct neurosurgical oversight is safe and implies a reduction in utilization of hospital resources.


Tartary buckwheat flavonoids alleviates high-fat diet induced kidney fibrosis in mice by inhibiting MAPK and TGF-β1/Smad signaling pathway.
Tartary buckwheat flavonoids (TBF) are active components extracted from Tartary buckwheat, which have abundant biological effects. According to this study, we investigated the effect of TBF on high-fat diet (HFD)-induced kidney fibrosis and its related mechanisms. In vivo, we established an HFD-induced kidney fibrosis model in mice and administered TBF. The results showed that TBF was able to alleviate kidney injury and inflammatory response. Subsequently, the mRNA levels between the HFD group and the TBF + HFD group were detected using RNA-seq assay. According to the gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) results, the differential genes were enriched in lipid metabolism and mitogen-activated protein kinases(MAPK) signaling pathways. We examined the protein expression of lipid metabolism-related pathways and the level of lipid metabolism. The results showed that TBF significantly activated the adenosine monophosphate activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) pathway and effectively reduced kidney total cholesterol (TC), triglyceride (TG) and low-density lipoproteinc cholesterol (LDL-C) levels and increased high-density lipoprotein cholesterol (HDL-C) levels in mice. TBF also inhibited transforming growth factor-β1/Smad (TGF-β1/Smad) and MAPK signaling pathways, thus slowing down the kidney fibrosis process. In vitro, using palmitic acid (PA) to stimulate TCMK-1 cells, the in vivo results similarly demonstrated that TBF could alleviate kidney fibrosis in HFD mice by inhibiting TGF1/Smad signaling pathway and MAPK signaling pathway.


Mobile health for cardiovascular risk management after cardiac surgery: results of a sub-analysis of The Box 2.0 study.
Lowering low-density lipoprotein (LDL-C) and blood pressure (BP) levels to guideline recommended values reduces the risk of major adverse cardiac events in patients who underwent coronary artery bypass grafting (CABG). To improve cardiovascular risk management, this study evaluated the effects of mobile health (mHealth) on BP and cholesterol levels in patients after standalone CABG. This study is a post hoc analysis of an observational cohort study among 228 adult patients who underwent standalone CABG surgery at a tertiary care hospital in The Netherlands. A total of 117 patients received standard care, and 111 patients underwent an mHealth intervention. This consisted of frequent BP and weight monitoring with regimen adjustment in case of high BP. Primary outcome was difference in systolic BP and LDL-C between baseline and value after three months of follow-up. Mean age in the intervention group was 62.7 years, 98 (88.3%) patients were male. A total of 26 449 mHealth measurements were recorded. At three months, systolic BP decreased by 7.0 mmHg [standard deviation (SD): 15.1] in the intervention group vs. -0.3 mmHg (SD: 17.6; P < 0.00001) in controls; body weight decreased by 1.76 kg (SD: 3.23) in the intervention group vs. -0.31 kg (SD: 2.55; P = 0.002) in controls. Serum LDL-C was significantly lower in the intervention group vs. controls (median: 1.8 vs. 2.0 mmol/L; P = 0.0002). This study showed an association between home monitoring after CABG and a reduction in systolic BP, body weight, and serum LDL-C. The causality of the association between the observed weight loss and decreased LDL-C in intervention group patients remains to be investigated.


Rate versus rhythm control in the management of patients with atrial fibrillation.
The management of patients with atrial fibrillation involves three main areas: anticoagulation, rate control and rhythm control. Importantly, these are not mutually exclusive of each other. Anticoagulation is necessary for patients who are at a high risk of stroke; for example, those who are older than 75 years, or those who have hypertension, severe left ventricular dysfunction, previous cerebrovascular events, or diabetes. It is now clear that patients who are at a high risk of stroke require long-term anticoagulation with warfarin regardless of whether a rate-control or rhythm-control strategy is chosen. One possible exception might be patients who are apparently cured with catheter ablation. Several published trials comparing rate-control and rhythm-control strategies for the treatment of patients with atrial fibrillation have shown no difference in mortality between these approaches. The patients enrolled in these studies were typically over 65 years of age. Data comparing rate and rhythm strategies in patients who are younger than 60 years of age are limited. For more elderly patients, it seems reasonable to consider rate control as a primary treatment option and to reserve rhythm control for those who do not respond to rate control. For younger patients, we prefer to start with a rhythm-control approach and to reserve rate-control approaches for patients in whom antiarrhythmic drugs, ablation, or both, do not ameliorate the symptoms.


Mammary carcinoma: toward a realistic mouse model of incurable cancers.
As long as breast cancer (BC) stays under immunosurveillance, it can be controlled by treatments eliciting anticancer immune responses. However, once BC escapes immunosurveillance, it becomes therapeutically uncontrollable. A paper in the Journal for ImmunoTherapy of Cancer describes a new hormone receptor-positive BC cell line generating incurable tumors in C57BL/6 mice.


INTERNAL LIMITING MEMBRANE PEELING DURING VITRECTOMY FOR DIABETIC VITREOUS HEMORRHAGE: A Randomized Clinical Trial.
To evaluate the benefits of internal limiting membrane peeling in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for the treatment of vitreous hemorrhage. Two hundred and fifty-eight proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for vitreous hemorrhage were enrolled into the trial. Patients were randomized into one of two cohorts: Group A patients underwent internal limiting membrane peeling, whereas Group B patients did not undergo internal limiting membrane peeling. The main outcome was best-corrected visual acuity at 6 months. Secondary outcomes were optical coherence tomography central macular thickness at 6 months, incidence of diabetic macular edema treatment during the postoperative trial period, and incidence of epiretinal membrane at 6 months. Two hundred and seven patients were randomized and completed 6 months follow-up. Group A had better best-corrected visual acuity at 6 months than Group B (P < 0.01). Group A had a lower incidence of diabetic macular edema treatment during the postoperative trial period and a lower incidence of epiretinal membrane at 6 months than Group B (P = 0.02 and P < 0.001, respectively). There was a trend toward lower central macular thickness on optical coherence tomography in Group A than Group B (P = 0.09). There were no significant differences in baseline details or complications intraoperatively or postoperatively between cohorts. This trial demonstrated better vision, fewer postoperative diabetic macular edema treatments, and a lower incidence of epiretinal membrane at 6 months when internal limiting membrane peeling was performed. Internal limiting membrane peeling may be considered a vital maneuver to perform in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy for vitreous hemorrhage.


[Emergencies in dermatology : From gonorrhea to angioedema].
The spectrum of dermatological emergencies is diverse. Infections, in particular sexually transmitted infections, anaphylactic reactions, and cutaneous drug reactions are common causes for patients to present themselves to the dermatological emergency service. If a sexually transmitted infection is suspected, it is important for the physician to recognize which diseases need immediate treatment to avoid late complications. This requires a reliable diagnosis and knowledge of the appropriate therapy. Cutaneous drug reactions can take many forms. There is a spectrum of reactions that occur immediately after the administration of a medication (which manifest themselves as anaphylaxis), to those that can appear weeks after the initiation of a therapy. These reactions can be harmless and self-limiting, but also be life-threatening. It is essential for physicians in everyday clinical practice to recognize drug intolerances in time and to treat them appropriately.


Differences in the distribution of F-actin in outer hair cells along the organ of Corti.
There is evidence of differences in the structure, innervation and physiological responses between outer hair cells (OHCs) of the basal and apical turns of the mammalian cochlea. In this study we have used rhodamine-labelled phalloidin to investigate the differential distribution of F-actin in OHCs along the organ of Corti of the guinea pig. Isolated OHCs and surface preparations and cryosections of the organ of Corti were studied. F-actin was observed in stereocilia and the cuticular plate of all OHCs. In addition, some OHCs had a network of F-actin extending from the cuticular plate towards the nucleus. This infracuticular network was observed in most OHCs of the apical cochlear turns but was not seen in any OHCs of the basal turn. These microstructural differences between OHCs of the base and apex could be related to differences in OHC function between the apical and basal portions of the cochlea.


Comparison of liquid-liquid extraction, solid-phase extraction and co-precipitation preconcentration methods for the determination of cadmium, copper, nickel, lead and zinc in seawater.
Three major types of pre-concentration methods were evaluated and optimised for the extraction and determination of Cd, Cu, Ni, Pb and Zn from seawater samples. The traditional APDC/DDDC-Freon liquid-liquid extraction method showed excellent results for a multi-elemental analysis. However, the technique is labour consuming, very sensitive to operational conditions, employs environmentally unsafe and expensive solvents and requires large sample volumes. In the solid phase extraction method, the performances of a traditional Amberlite XAD-4 and a novel Dowex Optipore V-493 were evaluated. Application of Dowex Optipore V-493 resin provided better results at low concentrations than the generally used Amberlite XAD-4 resin using low sample volumes. However, the presence of natural organic compounds may decrease extraction efficiency of both resins for Cu. Thus, a pre-treatment with UV irradiation is advantageous for samples with high organic content. Cobalt co-precipitation methods showed good Cu and Ni recoveries, but gave poor results for Cd at low concentrations. In addition, high sample volumes are required. Both solid phase and co-precipitation methods showed unsatisfactory results in determination of Pb. Finally, a summary of methods advantages are given for choosing the most suitable method.


Quantitative electric field mapping of a p-n junction by DPC STEM.
Local electromagnetic fields in a specimen is measured at high spatial resolutions using differential phase contrast (DPC) imaging in scanning transmission electron microscopy (STEM). According to previous studies, DPC signals can be quantified by measuring the center of mass of the diffraction pattern intensity and/or performing a deconvolution method based on a phase contrast transfer function (PCTF). However, when using a segmented detector, the field strength has been considerably underestimated for a very thick specimen. The main cause of the underestimation is assumed to be inelastic scattering, mainly bulk plasmon scattering. In this study, we develop a method to remove this inelastic scattering effect from segmented detector DPC signals by modifying the PCTF deconvolution method. Field quantification results using this new technique are compared with those using pixelated detector DPC and electron holography, and all results indicated good agreement within an error margin.


Morbidity following isolated fractures of the sacrum.
There is little information in the orthopaedic literature on the long-term results following isolated fractures of the sacrum. The present study traced patients with these fractures, and attempted to identify the incidence of long-term symptoms. The study revealed that isolated fractures of the sacrum are not always benign, and may result in chronic discomfort (sacrodynia) or persistent neurological symptoms.


Evaluation of posterior subcapsular cataracts. With spatial contrast acuity.
A new microcomputer-controlled instrument that tests contrast acuity is described. It displays a range of Sloan optotype sets at five different levels between 3 and 95% contrast. The spatial contrast acuities of two groups were compared with this instrument. The first group consisted of 68 eyes of patients with posterior subcapsular cataracts whose conventional, high-contrast visual acuity was 20/60 or better. The second group was comprised of 146 eyes with normal vision. The posterior subcapsular cataract group had greater variation in visual performance and a more pronounced decrease in spatial acuity at lower contrasts than did the normal group. This study indicates that high-contrast acuity measurements, in patients with posterior subcapsular cataracts, do not predict acuity at other contrast levels.


Effects of vegetation densities on the performance of attractive targeted sugar baits (ATSBs) for malaria vector control: a semi-field study.
Attractive targeted sugar baits (ATSBs) control sugar-feeding mosquitoes with oral toxicants, and may effectively complement core malaria interventions, such as insecticide-treated nets even where pyrethroid-resistance is widespread. The technology is particularly efficacious in arid and semi-arid areas. However, their performance remains poorly-understood in tropical areas with year-round malaria transmission, and where the abundant vegetation constitutes competitive sugar sources for mosquitoes. This study compared the efficacies of ATSBs (active ingredient: 2% boric acid) in controlled settings with different vegetation densities. Potted mosquito-friendly plants were introduced inside semi-field chambers (9.6 m by 9.6 m) to simulate densely-vegetated, sparsely-vegetated, and bare sites without any vegetation (two chambers/category). All chambers had volunteer-occupied huts. Laboratory-reared Anopheles arabiensis were released nightly (200/chamber) and host-seeking females recaptured using human landing catches outdoors (8.00 p.m.-9.00 p.m.) and CDC-light traps indoors (9.00 p.m.-6.00 a.m.). Additionally, resting mosquitoes were collected indoors and outdoors each morning using Prokopack aspirators. The experiments included a "before-and-after" set-up (with pre-ATSBs, ATSBs and post-ATSBs phases per chamber), and a "treatment vs. control" set-up (where similar chambers had ATSBs or no ATSBs). The experiments lasted 84 trap-nights. In the initial tests when all chambers had no vegetation, the ATSBs reduced outdoor-biting by 69.7%, indoor-biting by 79.8% and resting mosquitoes by 92.8%. In tests evaluating impact of vegetation, the efficacy of ATSBs against host-seeking mosquitoes was high in bare chambers (outdoors: 64.1% reduction; indoors: 46.8%) but modest or low in sparsely-vegetated (outdoors: 34.5%; indoors: 26.2%) and densely-vegetated chambers (outdoors: 25.4%; indoors: 16.1%). Against resting mosquitoes, the ATSBs performed modestly across settings (non-vegetated chambers: 37.5% outdoors and 38.7% indoors; sparsely-vegetated: 42.9% outdoors and 37.5% indoors; densely-vegetated: 45.5% outdoors and 37.5% indoors). Vegetation significantly reduced the ATSBs efficacies against outdoor-biting and indoor-biting mosquitoes but not resting mosquitoes. While vegetation can influence the performance of ATSBs, the devices remain modestly efficacious in both sparsely-vegetated and densely-vegetated settings. Higher efficacies may occur in places with minimal or completely no vegetation, but such environments are naturally unlikely to sustain Anopheles populations or malaria transmission in the first place. Field studies therefore remain necessary to validate the efficacies of ATSBs in the tropics.


Neutrophil adherence receptor deficiency regressing with granulocyte-colony stimulating factor therapy in a case of glycogen storage disease type Ib.
Neutrophils from patients suffering from glycogen storage disease type Ib (GSD-Ib) show marked functional deficiencies (chemotaxis, respiratory burst, and phagocytosis). Here we describe neutrophil adherence receptor (L-selectin CD62L and beta2 integrins CD11b/CD18) deficiency in a patient with genotype of GSD-Ib, who presented with recurrent infections, diminished neutrophil count and impaired functions. Treatment with granulocyte-colony stimulating factor (G-CSF) had a beneficial effect on the infectious status, the enhancement of phagocytosis and the regression of the adherence receptor defect. this is the first observation of a patient with glycogen storage disease type Ib with a deficiency in leucocyte adherence receptor expression, which regressed with growth factor therapy. It underlines the potential role of these receptors in the genesis of recurrent infections which occur in patients with this disease.


Cingulate cortex function and multi-modal connectivity mapped using intracranial stimulation.
The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy. We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex's network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient's anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection. Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex.


Immortal time bias and survival in patients who self-monitor blood glucose in the Retrolective Study: self-monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes (ROSSO).
In the February 2006 issue of Diabetologia, the observational Retrolective Study: Self-monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes (ROSSO) reported a 51% reduction in the risk of all-cause mortality in patients with type 2 diabetes who performed self-monitoring of blood glucose (SMBG). However, these impressive benefits conflict with results from observational studies and randomised controlled trials. We aimed to show that these findings are caused by a flawed design that introduced immortal time bias. We illustrate the bias in the ROSSO study and demonstrate that it is large enough to completely explain the apparently protective effect of SMBG on all-cause mortality. In the ROSSO study, patients were classified as exposed to SMBG for their whole follow-up time if they performed self-monitoring for at least 1 year during the study period. Thus, the time between cohort entry and the date after 1 year self-monitoring was performed is unavoidably 'immortal' for patients with SMBG. Patients had to survive at least 1 year to be classified as exposed to this intervention and were artificially 'protected' from death. Based on published information, the total amount of misclassified immortal person-time in the SMBG group is at least 5,082 of 9,248 person-years at risk (55%). After re-classification of immortal person-time as unexposed, the unadjusted relative risk changed from 0.59 to 1.95. The apparently protective effect of SMBG on all-cause mortality observed in the ROSSO study is completely explained by immortal time bias.


Efficiency of biodegradable EDDS, NTA and APAM on enhancing the phytoextraction of cadmium by Siegesbeckia orientalis L. grown in Cd-contaminated soils.
Chelant assisted phytoextraction has been proposed to enhance the efficiency of remediation. This study evaluated the effects of biodegradable ethylene diamine tetraacetate (EDDS), nitrilotriacetic (NTA) and anionic polyacrylamide (APAM) on the tolerance and uptake of Siegesbeckia orientalis L. at 10 and 100 mg kg(-1) Cd-contaminated soils. On the 80th and 90th days of transplanting, pots were treated with EDDS and NTA at 0 (control), 1 and 2 mmol kg(-1) soils, and APAM at 0 (control), 0.07 and 0.14 g kg(-1). Generally, the root and shoot biomass of S. orientalis in all treatments reduced not significantly compared with the control, and the activities of peroxidase and catalase in leaves generally increased by the application of chelants (P<0.05). The concentrations of Cd in the shoots were increased significantly by addition of all chelants. As a result, the Cd accumulation of S. orientalis under treatments with higher dosages of the three chelants on the 80th day were 1.40-2.10-fold and 1.12-1.25-fold compared to control at 10 and 100 mg kg(-1) Cd, respectively. Under the addition of 2 mmol kg(-1) NTA on the 80th day, the highest metal extraction ratio reached 1.2% and 0.4% at 10 and 100 mg kg(-1) Cd soils, respectively. Therefore, the applications of EDDS, NTA and APAM may provide more efficient choices in chemical-enhanced phytoextraction.


Robust silver-mediated imidazolo-dC base pairs in metal DNA: dinuclear silver bridges with exceptional stability in double helices with parallel and antiparallel strand orientation.
A new unprecedented metal-mediated base pair was designed that stabilizes reverse Watson-Crick DNA (parallel strand orientation, ps) as well as canonical Watson-Crick DNA (antiparallel strand orientation, aps). This base pair contains two imidazolo-dC units decorated with furan residues. Tm measurements and spectroscopic studies reveal that each silver-mediated furano-imidazolo-dC forms exceptionally stable duplexes with ps and aps chain orientation. This stability increase by a silver-mediated base pair is the highest reported so far for ps and aps DNA helices.


Bone mass measurement: prediction of risk.
Accurate assessment of individual fracture risk requires measurement of bone mass (density). Another strong risk factor for identifying women or men who will develop fractures in the near future is the presence of previous (spine and nonspine) fractures. However, the occurrence of a low-trauma fracture almost anywhere in the skeleton is indicative of a more advanced stage of disease and is associated with a substantial, further increase in fracture risk, independent of bone mass. Thus, prevention of the first fracture should receive priority. In a clinical setting, initial assessment of bone mass can be combined with other, known risk factors and projected over the patient's remaining life expectancy, to estimate future, cumulative fracture probability. Estimates such as "remaining lifetime fracture probability" can also approximate the impact and cost-effectiveness of treatment, allowing for more objective and rational therapeutic planning for individual patients.


Mitochondrial dysfunctions, oxidative stress and neuroinflammation as therapeutic targets for neurodegenerative diseases: An update on current advances and impediments.
Neurodegenerative diseases (NDs) such as Alzheimer disease (AD), Parkinson disease (PD), and Huntington disease (HD) represent a major socio-economic challenge in view of their high prevalence yet poor treatment outcomes affecting quality of life. The major challenge in drug development for these NDs is insufficient clarity about the mechanisms involved in pathogenesis and pathophysiology. Mitochondrial dysfunction, oxidative stress and inflammation are common pathways that are linked to neuronal abnormalities and initiation of these diseases. Thus, elucidating the shared initial molecular and cellular mechanisms is crucial for recognizing novel remedial targets, and developing therapeutics to impede or stop disease progression. In this context, use of multifunctional compounds at early stages of disease development unclogs new avenues as it acts on act on multiple targets in comparison to single target concept. In this review, we summarize overview of the major findings and advancements in recent years focusing on shared mechanisms for better understanding might become beneficial in searching more potent pharmacological interventions thereby reducing the onset or severity of various NDs.


Pre-bypass morphological changes in vein grafts.
Random vein samples taken prior to bypass surgery have shown certain pathological features. Long saphenous vein was taken from the groin (proximal) and knee to mid-calf (distal) of 85 patients undergoing femoro-distal bypass over a 2-year period. During this period only four patients had cephalic arm vein used; this was also studied. Histological examination was performed using haematoxylin and eosin and van Geison stains. Intimal hyperplasia was seen in 62 (73%) proximal and 74 (87%) distal samples. There were significantly more distal veins with moderate to severe focal hyperplasia and circular muscle hypertrophy (p < 0.05 and p < 0.001). Changes of diffuse intimal hyperplasia were seen in three of the cephalic veins. Muscle hypertrophy occurred in 58 (68%) of proximal segments compared to 75 (88%) of distal segments (p < 0.005). This study shows that significant pathological changes are seen in long saphenous and cephalic veins thought to be "normal". These changes are more evident in the distal long saphenous vein. These changes may have a significant effect on the outcome of vein bypass.


Cyclosporine A loaded brain targeting nanoparticle to treat cerebral ischemia/reperfusion injury in mice.
Ischemic stroke is one of the main causes of death and disability in the world. The treatment for ischemic stroke is to restore blood perfusion as soon as possible. However, when ischemic brain tissue is re-perfused by blood, the mitochondrial permeability transition pore (mPTP) in neuron and microglia is excessively opened, resulting in the apoptosis of neuron and nerve inflammation. This aggravates nerve injury. Cyclosporine A (CsA) inhibits the over-opening of mPTP, subsequently reducing the release of ROS and the apoptosis of cerebral ischemia/reperfusion injured neuron and microglia. However, CsA is insoluble in water and present in high concentrations in lymphatic tissue. Herein, cerebral infarction tissue targeted nanoparticle (CsA@HFn) was developed to treat cerebral ischemia/reperfusion injury. CsA@HFn efficiently penetrated the blood-brain barrier (BBB) and selectively accumulated in ischemic area, inhibiting the opening of mPTP and ROS production in neuron. This subsequently reduced the apoptosis of neuron and the damage of BBB. Consequently, CsA@HFn significantly reduced the infarct area. Moreover, CsA@HFn inhibited the recruitment of astrocytes and microglia in ischemic region and polarized microglia into M2 type microglia, which subsequently alleviated the nerve inflammation. CsA@HFn showed a significant therapeutic effect on cerebral ischemia/reperfusion injury by alleviating the apoptosis of neuron, nerve inflammation and the damage of BBB in ischemic area. CsA@HFn has great potential in the treatment of ischemic stroke.


Development and psychometric validation of a new patient satisfaction instrument: the osteoARthritis Treatment Satisfaction (ARTS) questionnaire.
Given the increasing interest in treatment satisfaction research and the lack of a specific questionnaire in osteoarthritis (OA), we developed and explored the psychometric properties of the osteoARthritis Treatment Satisfaction (ARTS) questionnaire. The ARTS questionnaire which consists of 18 items was developed in French following the analysis of semi-structured interviews performed among 20 OA participants, five rheumatologists and five general practitioners. Psychometric properties were assessed in France on a cross-sectional sample of 797 OA participants and test-retest reliability was evaluated in an independent sample of 111 clinically stable OA participants who filled-in the questionnaire within a 7.7 (+/- 3.1) day interval. Using principal component analysis, four scales were identified: Treatment advantages (seven items), Treatment convenience (three items), Treatment confidence (two items) and Satisfaction with physician (six items). Item convergent and item discriminant validity were satisfactory. Internal consistency provided evidence of reliability and lack of redundancy (Cronbach's alphas ranged from 0.66 to 0.86). Test-retest reliability was acceptable for two out of four scales (intraclass correlations coefficients (ICC) ranged from 0.61 to 0.75). Significant between groups differences were found on the ARTS scales, demonstrating the known groups validity of the ARTS questionnaire. The responsiveness of the ARTS is still to be documented.


Bilateral Ureteral Obstruction Caused by Stone Formation After Laparoscopic Appendectomy in Children.
In children, urologic complications are rare after laparoscopic appendectomy (LA). In this article, we report the case of a 9-year-old boy with bilateral hydronephrosis caused by ureteral calculi 10 days after he had undergone LA. The patient's urinary output normalized and renal function recovered after stone extraction and bilateral ureteral stent insertion.


Socioeconomic and racial/ethnic spatial polarization and incarceration among people who inject drugs in 19 US metropolitan areas, 2015.
The purpose of this study is to test, for the first time, the association between spatial social polarization and incarceration among people who inject drugs (PWID) in 19 large U.S. metropolitan statistical areas (MSAs) in 2015. PWID were recruited from MSAs for the Centers for Disease Control and Prevention's 2015 National HIV Behavioral Surveillance. Administrative data were used to describe the ZIP-code areas, counties, and MSAs where PWID lived. We operationalized spatial polarization using the Index of Concentration at the Extremes (ICE), a measure that reflects polarization in race and household income at the ZIP-code level. We tested the association between spatial polarization and odds of past-year arrest and detainment using multilevel multivariable models. We found 37% of the sample reported being incarcerated in the past year. Report of past-year incarceration varied by race/ethnicity: 45% of non-Hispanic white PWID reported past-year incarceration, as did 25% of non-Hispanic Black PWID, and 43% of Hispanic/Latino PWID (N = 9047). Adjusted odds ratios suggest that Black PWID living in ZIP-code areas with a higher ICE score, meaning more white and affluent, had higher odds of past-year incarceration, compared to white PWID. In previous research, incarceration has been found to be associated with HIV acquisition and can deter PWID from engaging in harm reduction activities.


[Kinematic transmission-coefficient and the four-bar-system as a function-parameter and a form model for the mandibular depression-apparatus in Teleostei (author's transl)].
Through chains of ligaments and bones, which can be reduced to four-bar-systems (fbs), contraction of the sternohyoid and of the opercular levator muscle result in mandibular depression. Comparatively the opercular fbs transmits movement more efficiently than the hyoid fbs which, consequently, transmits force more efficiently.


Manganese enhances DNA- or RNA-mediated innate immune response by inducing phosphorylation of TANK-binding kinase 1.
Trace metals are essential for various physiological processes, but their roles in innate immunity have not been fully explored. Here, we found that manganese (Mn) significantly enhanced DNA-mediated IFN-α, IFN-β, and IFN-λ1 production. Microarray analysis demonstrated Mn highly upregulated 351 genes, which were involved in multiple biological functions related to innate immune response. Moreover, we found that Mn2+ alone activates phosphorylation of TANK-binding kinase 1 (TBK1). Inhibiting ataxia telangiectasia mutated (ATM) kinase using ATM inhibitor or siRNA suppressed Mn-enhanced DNA-mediated immune response with decreasing phosphorylation of TBK-1, suggesting that ATM involves in Mn-dependent phosphorylation of TBK1. Given that TBK1 is an essential mediator in DNA- or RNA-mediated signaling pathways, we further demonstrated that Mn2+ suppressed infection of HSV-1 (DNA virus) or Sendai virus (RNA virus) into human macrophages by enhancing antiviral immunity. Our finding highlights a beneficial role of Mn in nucleic-acid-based preventive or therapeutic reagents against infectious diseases.


Evaluation of a digital oral health intervention (Know Your OQ™) to enhance knowledge, attitudes and practices related to oral health.
Optimal oral health behaviours are crucial to avoid preventable dental diseases and maintain good oral health. This research aimed to evaluate the impact of a digital oral health intervention (Know Your OQ™) in changing knowledge, attitudes and practices related to oral health. Two studies were conducted with a total of 296 healthy adults. Demographic data as well as knowledge, attitudes, and practices (KAPs) related to oral health were collected before and after completion of the Know Your OQ™ intervention. The KAPs questionnaire included 19 multiple choice questions. Comprehension and feedback were also collected. In total, 134 (45%) male and 162 (55%) female participants completed the two studies. Across both studies, 5 out of 7 knowledge questions and 2 out of 5 attitude questions showed significant changes pre/post-intervention with participants increasing their knowledge and improving their attitudes towards oral health. Only 1 practice changed in the first study, however, in the second study, 4 out of 7 practice questions showed significant changes pre/post-intervention. Comprehensibility was high across both studies with overall, positive feedback on the intervention. A digital oral health intervention was successful in increasing knowledge, changing attitudes and self-reported practices with regards to oral health in a diverse sample of the US population.


The DNA methylation landscape of CD4+ T cells in oligoarticular juvenile idiopathic arthritis.
Juvenile idiopathic arthritis (JIA) is presumed to be driven by an adverse combination of genes and environment. Epigenetic processes, including DNA methylation, act as a conduit through which the environment can regulate gene activity. Altered DNA methylation has been associated with adult autoimmune rheumatic diseases such as rheumatoid arthritis, but studies are lacking for paediatric autoimmune rheumatic diseases including JIA. Here, we performed a genome-scale case-control analysis of CD4+ T cell DNA methylation from 56 oligoarticular JIA (oJIA) cases and 57 age and sex matched controls using Illumina HumanMethylation450 arrays. DNA methylation at each array probe was tested for association with oJIA using RUV (Remove Unwanted Variation) together with a moderated t-test. Further to this 'all-inclusive' analysis, we stratified by age at diagnosis (≤6yrs, >6yrs) and by sex as potential sources of heterogeneity. Following False Discovery Rate (FDR) adjustment, no probes were associated with oJIA in the all-inclusive, >6yrs-diagnosed, or sex-stratified analyses, and only one probe was associated with oJIA in the ≤6yrs-diagnosed analysis. We attempted technical validation and replication of 14 probes (punadj<0.01) at genes of known/potential relevance to disease. At VPS53, we demonstrated a regional shift towards higher methylation in oJIA (all-inclusive) compared to controls. At REEP3, where polymorphism has been previously associated with JIA, we demonstrated higher DNA methylation in male oJIA compared to male controls. This is the most comprehensive JIA case-control analysis of DNA methylation to date. While we have generated some evidence of altered methylation in oJIA, substantial differences are not apparent in CD4+ T cells. This may indicate a lesser relevance of DNA methylation levels in childhood, compared to adult, rheumatic disease.


Do "central sensitization" questionnaires reflect measures of nociceptive sensitization or psychological constructs? Protocol for a systematic review.
Central sensitization (CS) was first defined in animal studies to be increased nociceptive responsiveness due to sensitization of neurons in the central nervous system, usually the result of prolonged nociceptive input or a disease state. Recently, the concept of CS has been adopted in clinical assessments of chronic pain, but its diagnosis in humans has expanded to include the enhancement of a wide range of nociceptive, sensory, and emotional responses. Many poorly understood pain disorders are referred to as "central sensitivity syndrome," a term associated with a broad range of hypervigilant sensory and emotional responses. Diagnosis often involves a review of medical records and an assessment of behaviour, emotional disposition, and overall sensitivity of a patient. Obviously, these assessments are unable to directly capture the responsiveness of nociceptive neurons. The purpose of this review is to ascertain whether self-report questionnaires associated with central sensitization and the diagnosis of central sensitivity syndrome are associated with enhanced nociceptive responses or whether they more validly measure sensitivity in a broader sense (ie, including emotional responses). Following the PRISMA guidelines, a detailed search of studies that involve the Central Sensitization Inventory or Pain Sensitivity Questionnaire correlated with either nociceptive sensory tests (quantitative sensory testing) or emotional hypervigilance (anxiety, depression, stress, etc) will be conducted on MEDLINE, PsychINFO, and Web of Science. The review is expected to synthesize correlations between sensitivity questionnaires and nociceptive or emotional sensitivity to determine whether these questionnaires reflect a broadened understanding of the term "central sensitization."


A novel comparative study for electrochemical urea biosensor design: Effect of different ferrite nanoparticles (MFe2O4, M: Cu, Co, Ni, Zn) in urease immobilized composite system.
A new enzymatic electrochemical biosensor has been developed with the PANI/Nafion composite system containing ferrite nanoparticles with four different transition metals. The ferrite nanoparticles containing copper, cobalt, nickel, and zinc metals were synthesized by the co-precipitation method and their surfaces were modified with tetraethoxysilane and (3-aminopropyl) triethoxysilane to obtain -NH2 function in order to develop the purposed sensing system. The modified and unmodified ferrite nanoparticles were characterized by physically, chemically, and morphologically. Ferrite nanoparticles with suitable for enzyme immobilization were integrated on the GCE surface and covered with PANI/Nafion. According toelectrochemical measurements, it was determined that copper ferrite nanoparticles, which have the lowest bandgap value, significantly increased the biosensor performance. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to monitor biosensor production and evaluate its performance. A detection limit of 0.17 µM and a wide linear range of 0.5-45.0 µM were obtained for the urea detection with the DPV method with the sensing system (Nf/PANI/CuF/Urs). The biosensor has been successfully applied to soil and milk samples with high accuracy. In addition, it has been determined that the proposed method has good reproducibility, selectivity, and stability.


Precession modulation of the South Pacific westerly wind belt over the past million years.
The southern westerly wind belt (SWW) interacts with the Antarctic Circumpolar Current and strongly impacts the Southern Ocean carbon budget, and Antarctic ice-sheet dynamics across glacial-interglacial cycles. We investigated precipitation-driven sediment input changes to the Southeast Pacific off the southern margin of the Atacama Desert over the past one million years, revealing strong precession (19/23-ka) cycles. Our simulations with 2 ocean-atmosphere general circulation models suggest that observed cyclic rainfall changes are linked to meridional shifts in water vapor transport from the tropical Pacific toward the southern Atacama Desert. These changes reflect a precessional modulation of the split in the austral winter South Pacific jet stream. For precession maxima, we infer significantly enhanced rainfall in the southern Atacama Desert due to a stronger South Pacific split jet with enhanced subtropical/subpolar jets, and a weaker midlatitude jet. Conversely, we derive dry conditions in northern Chile related to reduced subtropical/subpolar jets and an enhanced midlatitude jet for precession minima. The presence of precessional cycles in the Pacific SWW, and lack thereof in other basins, indicate that orbital-scale changes of the SWW were not zonally homogeneous across the Southern Hemisphere, in contrast to the hemispherewide shifts of the SWW suggested for glacial terminations. The strengthening of the jet is unique to the South Pacific realm and might have affected winter-controlled changes in the mixed layer depth, the formation of intermediate water, and the buildup of sea-ice around Antarctica, with implications for the global overturning circulation and the oceanic storage of atmospheric CO2.


A case of nodular fasciitis that was difficult to distinguish from sarcoma.
Nodular fasciitis is a reactive proliferative lesion. It is often difficult to distinguish from sarcoma, such as malignant peripheral nerve sheath tumor (MPNST). Therefore, both pathological findings and clinical features must be considered. A 75-year-old man presented with a 1 × 1 cm mass on his left forearm that had enlarged rapidly without specific symptoms. Magnetic resonance imaging revealed a mass adjacent to brachioradialis. The lesion showed iso-intensity to muscle on T1-weighted images and hyperintensity on T2-weighted images. We made a clinical diagnosis of nodular fasciitis. Under observation, the mass gradually decreased in size and disappeared after two months. Four years later, another lesion appeared at the same site. We performed total excisional biopsy and histopathological examination indicated low grade MPNST or recurrent nodular fasciitis. Since malignancy could not be excluded, wide resection was performed. At 4 years postoperatively, there has been no recurrence. In this patient, nodular fasciitis of the right forearm was diagnosed clinically and showed spontaneous regression. However, recurrence was noted after four years. While the clinical features suggested recurrent nodular fasciitis, pathological findings indicated the possibility of low grade MPNST. When it is difficult to determine whether a lesion such as nodular fasciitis is benign or malignant, the patient should be managed by considering the possibility of malignancy.


Invadopodia: specialized cell structures for cancer invasion.
The spread of cancer cells to distant sites in the body is the major cause of cancer patient death. Growing evidence connects specialized subcellular structures, invadopodia, to cancer invasion and metastasis. Invadopodia, or invasive foot processes, are actin-rich protrusions that localize matrix-degrading activity to cell-substratum contact points and represent sites where cell signaling, proteolytic, adhesive, cytoskeletal, and membrane trafficking pathways physically converge. Understanding how invadopodia form and function should aid in the identification of novel targets for anti-invasive therapy.


Structure-activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells.
The organosulfur compound ajoene derived from the rearrangement of allicin found in crushed garlic can inhibit the proliferation of tumour cells by inducing G(2)/M cell cycle arrest and apoptosis. We report on the application of a concise four-step synthesis (Hunter et al., 2008 [1]) that allows access to ajoene analogues with the end allyl groups substituted. A library of twelve such derivatives tested for their anti-proliferation activity against WHCO1 oesophageal cancer cells has identified a derivative containing p-methoxybenzyl (PMB)-substituted end groups that is twelve times more active than Z-ajoene, with an IC(50) of 2.1μM (Kaschula et al., 2011 [2]). Structure-activity studies involving modification of the sulfoxide and vinyl disulfide groups of this lead have revealed that the disulfide is the ajoene pharmacophore responsible for inhibiting WHCO1 cell growth, inducing G(2)/M cell cycle arrest and apoptosis by caspase-3 activation, and that the vinyl group serves to enhance the anti-proliferation activity a further eightfold. Reaction of the lead with cysteine in refluxing THF as a model reaction for ajoene's mechanism of action based on a thiol/disulfide exchange reveals that the allylic sulfur of the vinyl disulfide is the site of thiol attack in the exchange.


Development of a computerised dental anxiety scale for children: validation and reliability.
To provide reliability and validity data on a computerised dental anxiety scale (the Smiley Faces Program or SFP) for children using faces as a response set. Five schools across Derby, Newcastle-upon-Tyne and Shropshire. The SFP was completed by 464 children (mean age 10.8 years). For validity purposes, 241 children also completed two other children's dental anxiety measures (the Modified Child Dental Anxiety Scale and the Dental Fear Survey). For test-retest purposes 100 of the children completed the SFP two weeks later. The SFP demonstrated good internal consistency (alpha = 0.8), test-retest reliability was good and significant correlations were found between the SFP and the other measures. The children rated the local anaesthetic and drill as the most anxiety-provoking items. This study suggests that the SFP is a valid and reliable measure for assessing children's trait dental anxiety and may help encourage dentists to formally assess dental anxiety.


Properties and specificity of the major metal-chelator-sensitive proteinase in the keratinolytic larvae of the webbing clothes moth.
The metal chelator-sensitive proteinase activity from the larvae of the webbing clothes moth, Tineola bisselliella, was fractionated into two components by chromatography on DEAE-cellulose and the properties of the major fraction investigated. The approximate molecular weight obtained by gel filtration was 24 000. The pH optimum of 9.4 and the high stability between pH 9.0 and 11.5 are consistent with the alkaline conditions known to be present in the larval mid-gut. The enzyme also showed a second region of high stability around pH 2.3. The cleavage specificity against S-carboxy-methyl A and B chains of insulin was quite different to that of the metal chelator-sensitive proteinases from snake venoms and microorganisms. 10 bonds in the A-chain and 8 bonds in the B-chain were cleaved and the tentative rules governing the specificity limitations of this metal-chelator-sensitive proteinase are discussed.


Medial versus lateral condyle bone mineral density ratios in a cross-sectional study: a potential marker for medial knee osteoarthritis severity.
To assess the association of bone mineral density (BMD) of the femoral and tibial condyles with knee pain and disease severity in women with symptomatic medial knee osteoarthritis (OA). We enrolled 192 women (ages 41-90 years) between April 2007 and March 2011. The subjects were divided into 2 groups according to joint space narrowing (JSN) on weight-bearing radiographs. BMD of the lumbar spine, proximal femur, and knee condyles was measured. Medial and lateral condyle BMDs of the femur and tibia as well as the medial versus lateral condyle BMD ratios were measured. Mean medial condyle BMDs, medial versus lateral condyle BMD ratios, and visual analog scale (VAS) pain in both the femur and the tibia were higher in the obliteration group compared with the narrowing group (P < 0.001 for all). A significant positive correlation was observed between the femoral and tibial condyles in the following parameters: medial condyle BMDs, lateral condyle BMDs, and medial versus lateral condyle BMD ratios (r = 0.791-0.844). In both the femur and the tibia, medial versus lateral condyle BMD ratios had significant positive correlations with femorotibial angle, medial osteophytes, lateral osteophytes, medial JSN, and VAS pain, and had significant negative correlations with the Knee Society pain and function scores. Although this study was a cross-sectional study, the femoral and tibial medial versus lateral condyle BMD ratios increased with more severe knee pain and might be a potential marker for monitoring disease severity in women with symptomatic medial knee OA.


Workload in rural practice: implications for education and health service structure.
In view of the reported maldistribution of medical manpower in Queensland, this study was undertaken to establish the effects of such a maldistribution on the workload and range of work performed by rural practioners. Rural practitioners were found to have a higher patient contact rate per week, and to perform more surgery and obstetrics than do their city counterparts.


CTLA4 (CD152) modulates the Th subset response and alters the course of experimental Leishmania major infection.
Since both the nature and the amplitude of an antigen-specific T cell response are dependent on co-stimulatory signals, we have investigated the role of CD28/CD152-mediated T cell co-stimulation in the regulation of experimental cutaneous leishmaniasis. CD28-deficient mice and their wild-type littermates are equally susceptible to Leishmania major infection. Whole anti-CD152 antibody significantly exacerbates the disease while anti-CD152 Fab ameliorates the disease in genetically susceptible BALB/c mice but not in C57BL/6, a resistant strain. The anti-CD152-induced exacerbation of the disease is accompanied by increased IL-4-secreting cell number, diminished parasite-specific delayed-type hypersensitivity (DTH) response and augmented anti-2,4,6-trinitrophenyl (TNP) IgG1 in response to TNP-leishmanial antigen crude soluble antigen (CSA), suggesting an exaggerated Th2 type of response. Anti-CD152 Fab-mediated amelioration of the disease is associated with increased IFN-gamma-secreting cell number, increased parasite-specific DTH response and enhanced IgG2a isotype in response to TNP-CSA suggesting a Th1 type of response. Unlike TNP-CSA, TNP-keyhole limpet hemocyanin does not induce the change in Ig isotype, indicating that the immunomodulatory effect of anti-CD152 is antigen specific. Anti-CD152 antibody-induced early change in Th subsets suggests an important role for CD152 in determining the course of L. major infection, perhaps by alteration of Th subset differentiation.


Effects of mazindol, fenfluramine and chlorimipramine on the 5-hydroxytryptamine uptake and storage mechanisms in rat brain: similarities and differences.
Mazindol and fenfluramine inhibited in vitro the uptake of 5-HT into rat forebrain synaptosomes, whether the synpatosomes were incubated in vitro with the drugs or obtained from animals pretreated in vitro. Chlorimipramine was also effective in this latter preparation. Dose-response relationships and time course of this effect for the various drugs were determined. Fenfluramine also caused release of 5-HT from preloaded synaptosomes in in vitro incubations. Mazindol did not. Brain 5-HT levels were measured after acute and chronic administration of mazindol, fenfluramine and chlorimipramine. Mazindol had no effect, fenfluramine was active in reducing brain 5-HT concentrations acutely and chlorimipramine only after chronic administration. Therefore, it seems that even a long lasting inhibition of the uptake, such as that induced by mazindol, is not sufficient, per se, to cause depletion of brain 5-HT.


Cerebrovascular segmentation and planning of depth electrode insertion for epilepsy surgery.
Depth electrodes are inserted in the brain to locate the epileptogenic zone without craniotomy, but there is risk of surgical hemorrhage. Preoperative planning is required to mitigate this risk. A preoperative imaging, segmentation and three dimensional (3D) visualization procedure was developed to provide neurosurgeons with cortical and vascular anatomy information for surgical planning and neuronavigation. Cerebral vascular imaging was performed with phase-contrast magnetic resonance angiography (PC-MRA). Fuzzy c-means was performed to extract brain parenchyma from the PC-MRA images. A multi-scale vessel enhancement filter and thresholding process were combined to segment the vasculature and suppress background noise in the PC-MRA images. Finally, 3D visualization of the vasculature and cortical structures was implemented using volume rendering. Quantitative and qualitative validation of the vascular segmentation method were done. Using manual vascular segmentation as the gold standard, our method produced a satisfactory result: sensitivity was as high as 90 % at a specificity level of 95 %. Moreover, comparing the 3D visualizations of the vasculature and cortical structure for 4 patients with their respective intraoperative craniotomy photographs showed high levels of similarity. A new automated segmentation and visualization procedure provides sufficient and accurate cortical and vascular anatomy information compared to intraoperative photographs. This method has potential to assist neurosurgeons with planning and neuronavigation for depth electrode insertion with avoidance of cerebral hemorrhage.


The Prevalence and Clinical Characteristics of Borderline Personality Disorder in South Korea Using National Health Insurance Service Customized Database.
The purpose of the present study was to identify the prevalence and clinical characteristics of borderline personality disorder (BPD) in South Korea using the Korean National Health Insurance database (DB). We used the National Health Insurance Service (NHIS)'s research DB (NHIS-2021-1-790) from January 1, 2010 to December 31, 2019, to make customized DB including sociodemographic information and absence or presence of BPD and other psychiatric disorders. The prevalence and the age of onset of BPD was estimated. To compare medical service utilization between the BPD group and the control group, a 1:1:1 propensity score matching was employed, and the regression analysis was conducted. The prevalence of BPD per 10000 people was 0.96 in 2010 and 1.06 in 2019. The prevalence ratio of males to females was 1:1.38 in 2010 and 1:1.65 in 2019, showing that BPD was more prevalent in females. The patients' overall average age of onset was 33.19±14.6 years, with the highest prevalence shown in 8503 people in their 20s. By administrative district, the highest prevalence of BPD per 10000 people was shown in Seoul with 8.71 and the lowest in Jeollanam-do with 2.35. The BPD patients showed a pattern of extensive use of general and mental healthcare services. This study identified the prevalence of BPD on a national DB set in South Korea. Although the prevalence of BPD in South Korea was relatively low compared to other countries, there was a steady increase in the number of BPD patients over a decade, which may be possibly due to an increased awareness of mental health and campaigns among healthcare providers and users in the country.


Renal transplantation in a patient with an artificial urinary sphincter device.
Use of the artificial urinary sphincter device has become widespread. We describe the successful transplantation of a renal allograft into a recipient with an artificial urinary sphincter. Pretransplant placement of a sphincter, intraoperative avoidance of the prosthetic device and proper urinary drainage perioperatively make the artificial urinary sphincter device a feasible means to provide continence in a renal transplant recipient.