Towards a new generation of agricultural system data, models and knowledge products: Information and communication technology.
Agricultural modeling has long suffered from fragmentation in model implementation. Many models are developed, there is much redundancy, models are often poorly coupled, model component re-use is rare, and it is frequently difficult to apply models to generate real solutions for the agricultural sector. To improve this situation, we argue that an open, self-sustained, and committed community is required to co-develop agricultural models and associated data and tools as a common resource. Such a community can benefit from recent developments in information and communications technology (ICT). We examine how such developments can be leveraged to design and implement the next generation of data, models, and decision support tools for agricultural production systems. Our objective is to assess relevant technologies for their maturity, expected development, and potential to benefit the agricultural modeling community. The technologies considered encompass methods for collaborative development and for involving stakeholders and users in development in a transdisciplinary manner. Our qualitative evaluation suggests that as an overall research challenge, the interoperability of data sources, modular granular open models, reference data sets for applications and specific user requirements analysis methodologies need to be addressed to allow agricultural modeling to enter in the big data era. This will enable much higher analytical capacities and the integrated use of new data sources. Overall agricultural systems modeling needs to rapidly adopt and absorb state-of-the-art data and ICT technologies with a focus on the needs of beneficiaries and on facilitating those who develop applications of their models. This adoption requires the widespread uptake of a set of best practices as standard operating procedures.


Health science education: reviewing a framework for problem-based learning.
Although problem-based learning (PBL) has become one pedagogical approach to gain currency in recent decades, its foundational underpinnings have remained obscure. This investigation seeks to elucidate the theoretical framework or assumptions upon which PBL operates. We have situated core PBL principles in the larger context of health science education, which underwent dramatic changes at the beginning of the twentieth century. The fundamental problem at that time in dental education was moving beyond a lecture-based and apprentice curriculum (students memorizing facts) to a critical thinking-based curriculum. We trace these developments and especially the principles that one thinker, who does not easily fit into any one school of thought, used to frame the problem. We found that the principles underlying the idea of PBL have existed for over a century in varying academic alleys outside of dentistry (including constructivist thought). Despite our technological advances, many of the core challenges of a century ago remain challenges today. Although PBL is certainly not the only way to provide dental students an opportunity to best develop critical thinking, it nevertheless provides an environment in which the learning process may be enhanced.


Normalization of hindbrain morphology after decompression of Chiari malformation Type I.
Chiari malformation Type I (CM-I) is characterized by hindbrain deformity. We investigated the effects of craniocervical decompression surgery on the anatomical features of hindbrain deformity with a prospective MRI study of patients with CM-I. A prospective longitudinal study was conducted in 48 patients with CM-I (39 with syringomyelia) treated with craniocervical decompression. Clinical examinations and cervical MRI were performed before surgery and 1 week, 3-6 months, and annually after surgery. Hindbrain deformity was defined by tonsillar ectopia, pointed cerebellar tonsils, and/or cervicomedullary protuberance. The length of the clivus, basiocciput (sphenooccipital synchondrosis to basion), supraocciput (internal occipital protuberance to opisthion), and anteroposterior (AP) width of CSF pathways at the foramen magnum were measured and compared with those from 18 healthy volunteers (control group). Before surgery, the patients' posterior fossa bones were short and their CSF pathways were narrow. All patients had tonsillar ectopia (mean [± SD] 12.3 ± 5.1 mm; normal 0.3 ± 1.0). The majority of patients had pointed tonsils and more than two-thirds exhibited a cervicomedullary protuberance. Clivus and basiocciput lengths were significantly shorter than the values obtained in the control group. However, the supraocciput length did not differ significantly from control measurements. The mean bulbopontine sulcus distance superior to the basion was 9.5 ± 2.6 mm (vs 13.6 ± 2.8 mm in controls; p < 0.0001). The AP widths of the CSF pathways at the level of the foramen magnum were significantly narrowed. After surgery, CSF pathways significantly expanded both ventrally and dorsally. By 3-6 months after surgery, pointed tonsils became round, cervicomedullary protuberance disappeared, and tonsillar ectopia diminished by 51% (to 6.0 ± 3.3 mm; p < 0.0001). The cerebellar tonsils and brainstem assumed a normal appearance within 6 months after craniocervical decompression. These findings support the concept that the CM-I is not a congenital malformation of the neural elements but rather an acquired malformation that arises from pulsatile impaction of the cerebellar tonsils into the foramen magnum. Clinical trial registration no.: NCT00001327.


Gene structure, alternate splicing, tissue distribution, cellular localization, and developmental expression pattern of mouse deubiquitinating enzyme isoforms Usp2-45 and Usp2-69.
We have identified a novel mouse gene, Usp2, encoding two ubiquitin-specific proteases (USPs) due to alternate splicing of 5' exons. Usp2-45 consists of 396 amino acids (45.2 kDa), while Usp2-69 is 619 amino acids (69.5 kDa). Usp2-69 results from the splicing of different combinations of untranslated 5' exons (1A, 1B, 1C) onto exon 1D and the 40-kDa catalytic core (exons 3-13), while Usp2-45 has exon 2 spliced onto the core. The catalytic core contains the highly conserved motifs of the UBP family of deubiquitinating enzymes. We can find no evidence for a reported 41-kDa isoform (UBP41) in any sequence databases. Usp2-69 is able to form a complex with Usp2-45 and with itself. Antibodies raised against the catalytic core recognized a 69-kDa protein, but did not detect a 45-kDa protein in mouse tissues. Using Northern blot, Western blot, and immunohistochemistry, Usp2 expression was observed in many adult and embryonic tissues including testis, heart, skeletal muscle, diaphragm, brain, kidney, liver, pancreas, lung, and skin. Both Usp2 isoforms were localized to the cytoplasm when overexpressed in COS-7 and NIH3T3 cells. The Usp2 expression pattern indicates that this protein might be involved in specific processes in different types of cells, especially those that are differentiating, and that its function is not restricted to a development of a particular organ.


An electrophysiological study of thalamo-caudate neurones in the cat.
Thalamo-caudate projection neurones were identified in cats by antidromic activation from the caudate nucleus, under chloralose anaesthesia or in cerveau isolé preparations. Units in nuclei centralis lateralis, medialis dorsalis, and centrum medianum-parafascicularis responded antidromically to one or more electrodes of a caudate nucleus array at latencies ranging from 0.4 to 16 ms. The responses did not appear to result from stimulus spread to the internal capsule. A separate population of medial thalamic units responded postsynaptically to caudate stimulation, at modal latency exceeding modal antidromic latency by 2 ms. Comparison of apparent conduction velocities for each thalamic nucleus indicated that the postsynaptic responses were activated by collaterals of thalamo-caudate neurones. A proportion of thalamo-caudate neurones responded to somatic stimulation; some of these were inhibited by caudate stimulation, and a few discharged on substantia nigra stimulation. These results demonstrate the possibility of somatic afferent and nigrofugal inputs to the caudate nucleus mediated by neurones of the medial thalamus.


Semi-automatic geographic atrophy segmentation for SD-OCT images.
Geographic atrophy (GA) is a condition that is associated with retinal thinning and loss of the retinal pigment epithelium (RPE) layer. It appears in advanced stages of non-exudative age-related macular degeneration (AMD) and can lead to vision loss. We present a semi-automated GA segmentation algorithm for spectral-domain optical coherence tomography (SD-OCT) images. The method first identifies and segments a surface between the RPE and the choroid to generate retinal projection images in which the projection region is restricted to a sub-volume of the retina where the presence of GA can be identified. Subsequently, a geometric active contour model is employed to automatically detect and segment the extent of GA in the projection images. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to qualitatively and quantitatively evaluate the proposed GA segmentation method. Experimental results suggest that the proposed algorithm can achieve high segmentation accuracy. The mean GA overlap ratios between our proposed method and outlines drawn in the SD-OCT scans, our method and outlines drawn in the fundus auto-fluorescence (FAF) images, and the commercial software (Carl Zeiss Meditec proprietary software, Cirrus version 6.0) and outlines drawn in FAF images were 72.60%, 65.88% and 59.83%, respectively.


Amino-terminal basic residues of Src mediate membrane binding through electrostatic interaction with acidic phospholipids.
Membrane targeting of pp60src (Src) is mediated by its myristoylated amino terminus. We demonstrate that, in addition to myristate, six basic residues in the amino terminus are essential for high-affinity binding to the lipid bilayer via electrostatic interaction with acidic phospholipids. Specifically, c-Src was shown to bind 2500-fold more strongly to vesicles composed of the physiological ratio of 2:1 phosphatidylcholine (PC)/phosphatidylserine (PS) than to neutral PC bilayer vesicles. The apparent Kd for binding of c-Src to the PC/PS bilayer was 6 x 10(-7) M. This interaction is sufficiently strong to account for c-Src membrane targeting. Mutants of c-Src in which the amino-terminal basic residues were replaced by neutral asparagine residues exhibited binding isotherms approaching that of wild-type binding to neutral bilayers (apparent Kd of 2 x 10(-3) M). The transforming v-Src and activated c-Src (Y527F) proteins also bound more strongly to PC/PS bilayers (apparent Kd of approximately 1 x 10(-5) M) than to neutral PC bilayers. In vivo experiments with Src mutants confirmed the role of positive charge in mediating membrane binding and cellular transformation.


Thyroid hormone signaling in energy homeostasis and energy metabolism.
The thyroid hormone (TH) plays a significant role in diverse processes related to growth, development, differentiation, and metabolism. TH signaling modulates energy expenditure through both central and peripheral pathways. At the cellular level, the TH exerts its effects after concerted mechanisms facilitate binding to the TH receptor. In the hypothalamus, signals from a range of metabolic pathways, including appetite, temperature, afferent stimuli via the autonomic nervous system, availability of energy substrates, hormones, and other biologically active molecules, converge to maintain plasma TH at the appropriate level to preserve energy homeostasis. At the tissue level, TH actions on metabolism are controlled by transmembrane transporters, deiodinases, and TH receptors. In the modern environment, humans are susceptible to an energy surplus, which has resulted in an obesity epidemic and, thus, understanding the contribution of the TH to cellular and organism metabolism is increasingly relevant.


Flexibility and constraints in the molt schedule of long-distance migratory shorebirds: causes and consequences.
Molt is a major component of the annual cycle of birds, the timing and extent of which can affect body condition, survival, and future reproductive success through carry-over effects. The way in which molt is fitted into the annual cycle seems to be a somewhat neglected area which is both of interest and of importance. Study of the causes of annual variation in the timing of molt and its potential consequence in long-distance migratory birds was examined using the Curlew Sandpiper, Calidris ferruginea, as a model species. Using the maximum likelihood molt models of Underhill and Zucchini (1988, Ibis 130:358-372), the relationship between annual variability in the start dates of molt at the population level with conditions on the breeding area was explored. Adult males typically started early in years when temperature in June on the Arctic breeding grounds were high compared to cold years while adult females molted later in years of high breeding success and/or warm July temperature and vice versa. When molt started later, the duration was often shorter, indicating that late completion of molt might have fitness consequences, probably jeopardizing survival. Evidence of this was seen in the low body condition of birds in years when molt was completed late. The results indicate that these migratory shorebirds follow a fine-tuned annual life cycle, and disturbances at a certain stage can alter next biological events through carry-over effects.


Renin suppression by saline is blunted in nonmodulating essential hypertension.
We have reported that 50% of subjects with normal renin essential hypertension have both delayed suppression of the renin-angiotensin-aldosterone axis following sodium infusion and a delayed rate of excretion of an acute salt load. In another study we have also described a subset of patients with essential hypertension (called nonmodulators) who have several abnormalities, including a pressor response to salt loading. To evaluate whether the abnormalities described in these different groups of patients actually occur in the same patient, we assessed the renin-angiotensin-aldosterone axis response to short-term saline loading in 38 hypertensive patients. Their ability to modulate was determined by their renal vascular response to infused angiotensin II on a high salt diet (200 mEq Na). In response to a 3-hour infusion of saline, 75 mEq/hr, the reduction in plasma renin activity at both 60 and 120 minutes was significantly greater (p less than 0.008) in patients with normal modulation than in the nonmodulators. Plasma aldosterone levels were also significantly lower (p less than 0.001) in those with intact modulation. Thus, nonmodulating essential hypertensive patients have abnormalities in several systems that influence sodium homeostasis, including altered adrenal and renal vascular response to angiotensin II, altered renal blood flow response to salt loading, and a delayed suppression of the renin-angiotensin-aldosterone system with short-term saline infusion.


miRViz: a novel webserver application to visualize and interpret microRNA datasets.
MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the regulation of major pathways in eukaryotic cells through their binding to and repression of multiple mRNAs. With high-throughput methodologies, various outcomes can be measured that produce long lists of miRNAs that are often difficult to interpret. A common question is: after differential expression or phenotypic screening of miRNA mimics, which miRNA should be chosen for further investigation? Here, we present miRViz (http://mirviz.prabi.fr/), a webserver application designed to visualize and interpret large miRNA datasets, with no need for programming skills. MiRViz has two main goals: (i) to help biologists to raise data-driven hypotheses and (ii) to share miRNA datasets in a straightforward way through publishable quality data representation, with emphasis on relevant groups of miRNAs. MiRViz can currently handle datasets from 11 eukaryotic species. We present real-case applications of miRViz, and provide both datasets and procedures to reproduce the corresponding figures. MiRViz offers rapid identification of miRNA families, as demonstrated here for the miRNA-320 family, which is significantly exported in exosomes of colon cancer cells. We also visually highlight a group of miRNAs associated with pluripotency that is particularly active in control of a breast cancer stem-cell population in culture.


Newborn screening for galactosaemia.
Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews.Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 18 December 2017.Date of the most recent search of additional resources: 11 October 2017. Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population. No studies of newborn screening for galactosaemia were found. No studies were identified for inclusion in the review. We were unable to identify any eligible studies for inclusion in this review and hence it is not possible to draw any conclusions based on randomised controlled studies. However, we are aware of uncontrolled studies which support the efficacy of newborn screening for galactosaemia. There are a number of reviews and economic analyses of non-trial literature suggesting that screening is appropriate.


Duplicated TLR5 of zebrafish functions as a heterodimeric receptor.
Toll-like receptor 5 (TLR5) of mammals, birds, and reptiles detects bacterial flagellin and signals as a homodimeric complex. Structural studies using truncated TLR5b of zebrafish confirm the homodimeric TLR5-flagellin interaction. Here we provide evidence that zebrafish (Danio rerio) TLR5 unexpectedly signals as a heterodimer composed of the duplicated gene products drTLR5b and drTLR5a. Flagellin-induced signaling by the zebrafish TLR5 heterodimer increased in the presence of the TLR trafficking chaperone UNC93B1. Targeted exchange of drTLR5b and drTLR5a regions revealed that TLR5 activation needs a heterodimeric configuration of the receptor ectodomain and cytoplasmic domain, consistent with ligand-induced changes in receptor conformation. Structure-guided substitution of the presumed principal flagellin-binding site in human TLR5 with corresponding zebrafish TLR5 residues abrogated human TLR5 activation, indicating a species-specific TLR5-flagellin interaction. Our findings indicate that the duplicated TLR5 of zebrafish underwent subfunctionalization through concerted coevolution to form a unique heterodimeric flagellin receptor that operates fundamentally differently from TLR5 of other species.


Relative susceptibility of Haeckeliania sperata (Hymenoptera: Trichogrammatidae) to pesticides used in citrus and ornamental systems in Florida.
Haeckeliania sperata Pinto is an egg-endoparasitoid of Diaprepes abbreviatus L. (Coleoptera: Curculionidae). We evaluated the relative susceptibility of H. sperata adults to commercially relevant pesticides used in citrus and ornamental production systems. Parasitoids were exposed to pesticide residues on leaf surfaces. Four concentrations of seven pesticides were tested; concentrations for each pesticide consisted of a dilution series using the label rate for field applications as the starting concentration. Lethal concentrations (LC50s and LC90s) were calculated 12 and 24 h after exposure to the pesticides. Lethal times (LT50s and LT90S) were estimated for each pesticide concentration. All tested pesticides had a negative effect on Haeckeliania's survivorship. However, some pesticides were significantly less harmful to this parasitoid. LC50s and LC90s of organophospate, carbamate, and pyrethroid pesticides were less than one eighth of the label rates. LT50s and LT90s of these insecticides were < 12 h even at the most diluted concentrations. Thus, applications of these pesticides might have a strong negative impact on the natural control of D. abbreviatus by H. sperata. Commercial formulations of imidacloprid, abamectin, petroleum oil, and a phosphonate fungicide allowed H. sperata to live longer compared with the previous pesticides, suggesting a certain degree of selectivity. Moreover, adults exposed to diluted concentrations of imidacloprid, abamectin, petroleum oil, and a phosphonate fungicide had a greater survival than those exposed to label concentrations. These findings suggest that the use of products that have less toxic effects on the introduced parasitoid will increase its chances to parasitize D. abbreviatus eggs.


The Association between Blunt Cardiac Injury and Isolated Sternal Fracture.
The treatment of isolated sternal fractures (ISF) throughout the world is heterogeneous. This study aimed to identify the incidence, morbidity, and mortality associated with isolated fractures of the sternum and describe current practice for diagnosis and management of ISF and cardiac injury at a level I trauma center in the UK. A retrospective cohort study of adult patients (>16 years) with ISF presenting from 2006 to 2010 was conducted. Eighty-eight patients with ISF were identified. Most patients (88%, 77) were admitted to hospital with 66% (58) of them discharged within 48 hours. Two (2%) patients had an ER EKG with abnormality but both resolved to normal sinus rhythm within 6 hours of follow-up. Serum CEs were drawn from 55 (63%) patients with only 2 (2%) having a rise in serum troponin >0.04; however, in both of these patients troponin quickly normalized. Six (7%) patients underwent echocardiograms without significant findings. In all 88 patients with ISF, no cases of clinically significant cardiac injury were identified. Patients presenting with an isolated sternal fracture with no changes on EKG or chest X-ray do not warrant an admission to hospital and may be discharged from the ER.


Cetuximab Plus Chemoradiotherapy for HIV-Associated Anal Carcinoma: A Phase II AIDS Malignancy Consortium Trial.
Purpose Squamous cell carcinoma of the anal canal (SCCAC) is characterized by high locoregional failure (LRF) rates after definitive chemoradiation (CRT), associated with anogenital human papilloma virus, and often appears in HIV infection. Because cetuximab enhances the effect of radiation therapy in human papilloma virus-associated oropharyngeal SCC, we hypothesized that adding cetuximab to CRT would reduce LRF in SCCAC. Methods Forty-five patients with stage I to III SCCAC and HIV infection received CRT: 45 to 54 Gy radiation therapy to the primary tumor and regional lymph nodes plus eight once-weekly doses of concurrent cetuximab and two cycles of cisplatin and fluorouracil. The study was designed to detect at least a 50% reduction in 3-year LRF rate (one-sided α, 0.10; power, 90%), assuming a 35% LRF rate from historical data. Results The 3-year LRF rate was 42% (95% CI, 28% to 56%; one-sided P = .9) by binomial proportional estimate using the prespecified end point (LRF or alive without LRF and followed < 3 years), and 20% (95% CI, 10% to 37%) by Kaplan-Meier estimate in post hoc analysis using definitions and methods consistent with historical data. Three-year rates by Kaplan-Meier estimate were 72% (95% CI, 56% to 84%) for progression-free survival and 79% (95% CI, 63% to 89%) for overall survival. Grade 4 toxicity occurred in 26%, and 4% had treatment-associated deaths. Conclusion HIV-associated SCCAC is potentially curable with definitive CRT. Although addition of cetuximab may result in less LRF, the 20% recurrence and 26% grade 4 toxicity rates indicate the continued need for more-effective and less-toxic therapies.


Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells.
Uvomorulin is a cell-adhesion molecule implicated in the compaction process of mouse preimplantation embryos and the aggregation of embryonal carcinoma cells. A rabbit antiserum against purified uvomorulin also reacts with epithelial cells of various adult tissues. In this study, we investigated the localization of uvomorulin on adult intestinal epithelial cells using electron microscopic analyses. Uvomorulin was shown to exhibit a highly restricted localization in the intermediate junctions of these cells. The results are discussed with respect to a possible adhesive function of uvomorulin on intestinal epithelial cells.


Relating Things and Stuff via ObjectProperty Interactions.
In the last few years, substantially different approaches have been adopted for segmenting and detecting "things" (object categories that have a well defined shape such as people and cars) and "stuff" (object categories which have an amorphous spatial extent such as grass and sky). While things have been typically detected by sliding window or Hough transform based methods, detection of stuff is generally formulated as a pixel or segment-wise classification problem. This paper proposes a framework for scene understanding that models both things and stuff using a common representation while preserving their distinct nature by using a property list. This representation allows us to enforce sophisticated geometric and semantic relationships between thing and stuff categories via property interactions in a single graphical model. We use the latest advances made in the field of discrete optimization to efficiently perform maximum a posteriori (MAP) inference in this model. We evaluate our method on the Stanford dataset by comparing it against state-of-the-art methods for object segmentation and detection. We also show that our method achieves competitive performances on the challenging PASCAL '09 segmentation dataset.


Overview of model validation for survival regression model with competing risks using melanoma study data.
The article introduces how to validate regression models in the analysis of competing risks. The prediction accuracy of competing risks regression models can be assessed by discrimination and calibration. The area under receiver operating characteristic curve (AUC) or Concordance-index, and calibration plots have been widely used as measures of discrimination and calibration, respectively. One-time splitting method can be used for randomly splitting original data into training and test datasets. However, this method reduces sample sizes of both training and testing datasets, and the results can be different by different splitting processes. Thus, the cross-validation method is more appealing. For time-to-event data, model validation is performed at each analysis time point. In this article, we review how to perform model validation using the riskRegression package in R, along with plotting a nomogram for competing risks regression models using the regplot() package.


Stabilisation of atherosclerotic plaques. Position paper of the European Society of Cardiology (ESC) Working Group on atherosclerosis and vascular biology.
Plaque rupture and subsequent thrombotic occlusion of the coronary artery account for as many as three quarters of myocardial infarctions. The concept of plaque stabilisation emerged about 20 years ago to explain the discrepancy between the reduction of cardiovascular events in patients receiving lipid lowering therapy and the small decrease seen in angiographic evaluation of atherosclerosis. Since then, the concept of a vulnerable plaque has received a lot of attention in basic and clinical research leading to a better understanding of the pathophysiology of the vulnerable plaque and acute coronary syndromes. From pathological and clinical observations, plaques that have recently ruptured have thin fibrous caps, large lipid cores, exhibit outward remodelling and invasion by vasa vasorum. Ruptured plaques are also focally inflamed and this may be a common denominator of the other pathological features. Plaques with similar characteristics, but which have not yet ruptured, are believed to be vulnerable to rupture. Experimental studies strongly support the validity of anti-inflammatory approaches to promote plaque stability. Unfortunately, reliable non-invasive methods for imaging and detection of such plaques are not yet readily available. There is a strong biological basis and supportive clinical evidence that low-density lipoprotein lowering with statins is useful for the stabilisation of vulnerable plaques. There is also some clinical evidence for the usefulness of antiplatelet agents, beta blockers and renin-angiotensin-aldosterone system inhibitors for plaque stabilisation. Determining the causes of plaque rupture and designing diagnostics and interventions to prevent them are urgent priorities for current basic and clinical research in cardiovascular area.


The cellular stimuli for the rejection of established islet allografts.
Previous work from our laboratory has indicated that the transplantation of pancreatic islets is a feasible approach to the problem of diabetes. A major obstacle to transplantation is presented by passenger leucocytes, which contaminate the preparations and can lead to the prompt rejection of fresh islets. We have extended our previous studies on the rejection of islet allografts by challenging transplanted animals with enriched lymphoid cell populations prepared from animals both syngeneic to the transplanted islets and third party. Rapid and complete rejection was observed when the challenge peritoneal exudate cell population was syngeneic with the transplanted islets; rejection was determined by both functional and histologic criteria. Peritoneal exudate cells from a third-party rat strain induced delayed and variable effects upon the function of the transplant. In contrast, splenic T-cells were capable of inducing rejection, regardless of the strain of origin, though the time course of T-cell-induced rejection was slower than that observed by syngeneic peritoneal exudate cells. Finally, splenic B-cells completely failed to induce rejection. Our data indicate that at least two mechanisms exist by which the rejection of islet allografts may be triggered. The first is a haplotype-specific mechanism initiated by a cell type present at high frequency in peritoneal exudate cells; these are probably macrophages. The second mechanism is initiated by immunocompetent T-cells; this mechanism shows no haplotype specificity. We suggest that both macrophages and T-cells must be considered when devising protocols for the removal of passenger leucocytes from allografts.


Signal processing method based on group delay calculation for distributed Bragg wavelength shift in optical frequency domain reflectometry.
A signal processing method based on group delay calculations is introduced for distributed measurements of long-length fiber Bragg gratings (FBGs) based on optical frequency domain reflectometry (OFDR). Bragg wavelength shifts in interfered signals of OFDR are regarded as group delay. By calculating group delay, the distribution of Bragg wavelength shifts is obtained with high computational efficiency. We introduce weighted averaging process for noise reduction. This method required only 3.5% of signal processing time which was necessary for conventional equivalent signal processing based on short-time Fourier transform. The method also showed high sensitivity to experimental signals where non-uniform strain distributions existed in a long-length FBG.


Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis.
To compare the effect of endoscopic ligation with that of sclerotherapy in the treatment of patients with bleeding esophageal varices. Strategies to identify published and unpublished research included searches of computerized bibliographic and scientific citations, review of citations in relevant primary articles, searches of services providing information on unpublished studies, contact with primary investigators and the ligation equipment manufacturer, and review of proceedings from pertinent scientific meetings. From 158 potentially relevant articles, duplicate independent review identified 7 relevant randomized trials that compared endoscopic ligation with sclerotherapy for the treatment of patients with bleeding esophageal varices. Independent, duplicate data abstraction of the population, intervention, outcome, and methodologic quality of the trials was done. Ligation therapy compared with sclerotherapy reduced the rebleeding rate (odds ratio, 0.52 [95% CI, 0.37 to 0.74]), the mortality rate (odds ratio, 0.67 [CI, 0.46 to 0.98]), and the rate of death due to bleeding (odds ratio, 0.49 [CI, 0.24 to 0.996]). Four patients would need to be treated with ligation instead of sclerotherapy to avert one rebleeding episode, and 10 would need to be treated with ligation instead of sclerotherapy to prevent one death. Esophageal strictures occurred less frequently with ligation (odds ratio, 0.10 [CI, 0.03 to 0.29]), but no significant differences were seen between treatments for pulmonary infections or bacterial peritonitis. Additionally, the number of endoscopic treatment sessions required to achieve variceal obliteration was lower with ligation than with sclerotherapy. On the basis of lower rates of rebleeding, mortality, and complications and the need for fewer endoscopic treatments, ligation should be considered the endoscopic treatment of choice for patients with esophageal variceal bleeding.


In search of a function for the most frequent naturally-occurring length polymorphism (MFNLP) of the HIV-1 LTR: retaining functional coupling, of Nef and RBF-2, at RBEIII?
Although the prototypical HIV-1 LTR sequences were determined 22 years ago from the initial isolate, elucidating which transcription factors are critical to replication in vivo, has been difficult. One approach has been to examine HIV-1 LTRs that have gone through the gamut of in vivo mutation and selection, in search of absolutely conserved sequences. In this vein, RBEIII sequences are virtually 100% conserved in naturally occurring HIV-1 LTRs. This is because when they are mutated, the MFNLP recreates an RBEIII site. Here, I enumerate some retroviral mutation mechanisms, which could generate the MFNLP. I then review the literature corresponding to the MFNLP, highlighting the discovery in 1999, that RBEIII and MFNLP sequences, bind USF and TFII-I cooperatively, within the context of earlier and later work that suggests a role in HIV-1 activation, through T-cell receptor engagement and the MAPK cascade. One exception to the nearly absolute conservation of RBEIII, has been a group of long term non progressors (LTNP). These patients harbor deletions to the Nef gene. However, the Nef gene overlaps with the LTR, and the LTNP deletions abrogate RBEIII, in the absence of an MFNLP. I suggest that the MFNLP retains functional coupling between the MAPK-mediated effects of Nef and the HIV-1 LTR, through RBEIII. I propose that difficult-to-revert-mutations, to either Nef or RBEIII, result in the convergent LTNP Nef/LTR deletions recently observed. The potential exploitation of this highly conserved protein-binding site, for chimeric transcription factor repression (CTFR) of HIV-1, functionally striving to emulate the LTNP deletions, is further discussed.


Collective doses and risks from dental radiology in Great Britain.
The continued expansion of dental radiology in Britain up to the end of 1981 is demonstrated, with a rate of increase much in excess of that seen for general medical radiography. Of the total of 7.8 X 10(6) dental X-ray examinations undertaken in 1981 approximately 6.7 X 10(6) were intra-oral, 1.5 X 10(5) were extra-oral and 9.1 X 10(5) were pantomographic. Weighted dose equivalents for typical examinations in each of these categories were calculated using specific weighting factors for the important "remainder" organs. Values of 20 muSv, 30 muSv and 80 muSv were obtained for intra-oral, extra-oral and pantomographic techniques, respectively, corresponding to risks of fatal malignancy of 0.33, 0.5 and 1.3 per million. The estimated collective weighted dose equivalent of 212 man Sv to the population of Britain from the current level of dental radiology is predicted to result in no more than about three extra cases of fatal cancer when the age- and sex-related opportunity for manifestation of radiation-induced cancers is taken into account.


Ursolic acid suppresses the biological function of osteosarcoma cells.
Osteosarcoma is a highly malignant tumour that occurs in adolescents. Upregulation or the constitutive activation of epidermal growth factor receptor (EGFR) is a hallmark of osteosarcoma. To investigate the effect of ursolic acid on the biological function of osteosarcoma, MTT assay was used to detect the effect of ursolic acid on the proliferation of HOS and MG63 cells, while flow cytometry was used to analyse the effect on the cell cycle and apoptosis. Transwell and Matrigel assays were used to detect the effect of ursolic acid on cell migration and invasion, respectively. Western blot analysis and reverse transcription-quantitative polymerase chain reaction were used to detect the effects of different concentrations of ursolic acid on EGFR signaling pathway-related proteins, cell cycle, apoptosis and cell migration-related proteins. After overexpression or silencing of EGFR, the effects of ursolic acid on EGFR pathway and cell biological function were subsequently detected, using the same methods. The present study identified that ursolic acid had inhibitory effects on the growth and metastatic ability of osteosarcoma cells by suppressing EGFR.


Central nervous system involvement in the autonomic responses to psychological distress.
Psychological distress can trigger acute coronary syndromes and sudden cardiac death in vulnerable patients. The primary pathophysiological mechanism that plays a role in stress-induced cardiac events involves the autonomic nervous system, particularly disproportional sympathetic activation and parasympathetic withdrawal. This article describes the relation between psychological distress and autonomic nervous system function, with a focus on subsequent adverse cardiovascular outcomes. The role of the central nervous system in these associations is addressed, and a systematic review is presented of studies examining the association between stress-induced central nervous system responses measured by neuroimaging techniques and autonomic nervous system activation. Results of the systematic review indicate that the primary brain areas involved in the autonomic component of the brain-heart association are the insula, medial prefrontal cortex, and cerebellum (based on 121 participants across three studies that fitted the inclusion criteria). Other areas involved in stress-induced autonomic modulation are the (anterior) cingulate cortex, parietal cortex, somatomotor cortex/precentral gyrus, and temporal cortex. The interaction between central and autonomic nervous system responses may have implications for further investigations of the brain-heart associations and mechanisms by which acute and chronic psychological distress increase the risk of myocardial infarction, cardiac arrhythmias, and sudden cardiac death.


Prevention of paraplegia associated with resection of extensive thoracic aneurysms.
A review of the literature suggests that paraplegia associated with thoracic aortic surgery is preventable if intraoperative hypotension is eliminated, the distal aorta perfused adequately, and the intercostal arteries below T-8 level preserved. A surgical technique has been developed that leaves the posterior aortic wall, preserving the intercostal arteries below the level of T-8, and interspersing a diagonally tailored prosthesis with the aid of left atrial-to-femoral arterial bypass without heparinization. Seven patients with extensive aneurysms involving the entire descending thoracic aorta were operated on successfully by this technique without neurological complications.


Mapping the Epidemiology of Kaposi Sarcoma and Non-Hodgkin Lymphoma Among Children in Sub-Saharan Africa: A Review.
Children with human immunodeficiency virus (HIV) have an increased risk of developing Kaposi Sarcoma (KS) and non-Hodgkin lymphoma (NHL) compared to HIV-negative children. We compiled currently published epidemiologic data on KS and NHL among children in sub-Saharan Africa (SSA). Among countries with available data, the median incidence of KS was 2.05/100,000 in the general pediatric population and 67.35/100,000 among HIV-infected children. The median incidence of NHL was 1.98/100,000 among the general pediatric population, while data on NHL incidence among HIV-infected children were lacking. Larger regional studies are needed to better address the dearth of epidemiologic information on pediatric KS and NHL in SSA.


Direct interaction between emerin and lamin A.
Emerin is the protein of the inner nuclear membrane that is affected by mutation in X-linked Emery-Dreifuss muscular dystrophy. The autosomal dominant form of the disease is caused by mutations in the lamin A/C gene. Several lines of circumstantial evidence have suggested an interaction of emerin with lamins in the nuclear lamina but direct interaction between the two proteins has not yet been demonstrated. We now demonstrate direct interaction between recombinant emerin and lamin A molecules using biomolecular interaction analysis (BIA) and monoclonal antibodies. An emerin-lamin A interaction system may be related in function to the LAP2-lamin B system at the inner nuclear rim.


Robotic surgery in gynecologic cancer.
The development of robotic technology has facilitated the application of minimally invasive techniques for complex operations in gynecologic oncology. The objective of this article is to review the published literature regarding robotic surgery and its application to gynecologic cancer. To date, 20 articles addressing radical hysterectomy, six articles of radical trachelectomy, seven articles of surgical procedure in advanced or recurrent cervical cancer, 14 articles of endometrial cancer staging, and two articles solely on ovarian cancer all performed robotically are published in the literature. The majority of publications on robotic surgery are still retrospective or descriptive in nature. However, the data for gynecologic cancer show comparable results of robotic surgery compared with laparoscopy or laparotomy in terms of blood loss, length of hospital stay, and complications. Computer-enhanced technology with its associated benefits appears to facilitate the surgical approach for technically challenging operations performed to treat selected cases of cervical, endometrial, and ovarian cancer as evidenced by the current literature. Continued research and clinical trials are needed to further elucidate the equivalence or superiority of robot-assisted surgery to conventional methods in terms of oncologic outcome and patients' quality of life.


Per-operative cerebral near-infrared spectroscopy (NIRS) predicts maternal hypotension during elective caesarean delivery in spinal anaesthesia.
Spinal anaesthesia-induced maternal hypotension is common during elective caesarean section. This study evaluated whether cerebral near-infrared spectroscopy predicts maternal hypotension, defined as a 25% reduction in systolic blood pressure or heart rate or presentation of clinical symptoms. Thirty-eight ASA I-II parturients scheduled for elective caesarean section with spinal anaesthesia were monitored by near-infrared spectroscopy for changes in cerebral oxygenation (ScO(2)) with the recordings blinded to the anaesthesiologist. There was a 5% decrease in ScO(2) (median 8%, interquartile range 5-11%) in all 22 patients who developed hypotension, whereas only 2 of 13 women who did not develop hypotension had a 5% decrease in ScO(2). Median time from a 5% decrease in ScO(2) to hypotension was 81 (interquartile range 30-281) s. The sensitivity of near-infrared spectroscopy to predict hypotension was 1.00, with a specificity 0.85 and a predictability of 0.91. The results demonstrate a relationship between ScO(2) and impending hypotension during low-dose spinal anaesthesia for elective caesarean section. We suggest that immediate measures are taken to stabilise blood pressure if the near-infrared spectroscopy determined cerebral oxygenation decreases by more than 5%.


Trace organics removal using three membrane bioreactor configurations: MBR, IFAS-MBR and MBMBR.
Seventeen pharmaceutically active compounds and 22 other trace organic pollutants were analysed regularly in the influent and permeate from a semi-real plant treating municipal wastewater. The plant was operated during 29 months with different configurations which basically differed in the type of biomass present in the system. These processes were the integrated fixed-film activated sludge membrane bioreactor (IFAS-MBR), which combined suspended and attached biomass, the moving bed membrane bioreactor (MBMBR) (only attached biomass) and the MBR (only suspended biomass). Moreover, removal rates were compared to those of the wastewater treatment plant (WWTP) operating nearby with conventional activated sludge treatment. Reverse osmosis (RO) was used after the pilot plant to improve removal rates. The highest elimination was found for the IFAS-MBR, especially for hormones (100% removal); this was attributed to the presence of biofilm, which may lead to different conditions (aerobic-anoxic-anaerobic) along its profile, which increases the degradation possibilities, and also to a higher sludge age of the biofilm, which allows complete acclimation to the contaminants. Operating conditions played an important role, high mixed liquor suspended solids (MLSS) and sludge retention time (SRT) being necessary to achieve these high removal rates. Although pharmaceuticals and linear alkylbenzene sulfonates showed high removal rates (65-100%), nonylphenols and phthalate could only be removed to 10-30%. RO significantly increased removal rates to 88% mean removal rate.


Infectious and inflammatory disorders of the circulatory system and stroke in childhood.
The role of infectious and inflammatory causes of stroke is much more significant in children than in adults. Conversely, that of atherosclerotic disease, ischaemic heart disease and hypertensive haemorrhages has a lesser prominence in children. Bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, or Neiserria meningitidis has been known to cause stroke in children. The mechanism appears to be the spread of meningeal inflammation to involve the walls of intracranial vessels, resulting in arterial thrombosis with ischaemia or rupture with haemorrhage. Other infections caused by atypical bacterial agents such as Mycoplasma tuberculosis and viral agents such as varicella-zoster virus have also been well documented as causes of stroke. Non-infectious, inflammatory causes of stroke, such as collagen vascular disease and primary angiitis of the central nervous system, have been reported in children as well as adults. In this review, we will focus on recent advances in the field of childhood stroke caused by infectious and inflammatory disorders.


Factors influencing the implementation of cardiovascular risk scoring in primary care: a mixed-method systematic review.
Cardiovascular disease (CVD) such as ischemic heart disease and stroke is the leading causes of death and disability globally with a growing burden in low and middle-income countries. A credible way of managing the incidence and prevalence of cardiovascular diseases is by reducing risk factors. This understanding has led to the development and recommendation for the clinical use of cardiovascular risk stratification tools. These tools enhance clinical decision-making. However, there is a lag in the implementation of these tools in most countries. This systematic review seeks to synthesise the current knowledge of the factors influencing the implementation of cardiovascular risk scoring in primary care settings. We searched bibliographic databases and grey literature for studies of any design relating to the topic. Titles, abstracts and full texts were independently assessed for eligibility by two reviewers. This was followed by quality assessment and data extraction. We analysed data using an integrated and best fit framework synthesis approach to identify these factors. Quantitative and qualitative forms of data were combined into a single mixed-methods synthesis. The Consolidated Framework for Implementation Research was used as the guiding tool and template for this analysis. Twenty-five studies (cross-sectional n = 12, qualitative n = 9 and mixed-methods n = 4) were included in this review. Twenty (80%) of these were conducted in high-income countries. Only four studies (16%) included patients as participants. This review reports on a total of eleven cardiovascular risk stratification tools. The factors influencing the implementation of cardiovascular risk scoring are related to clinical setting and healthcare system (resources, priorities, practice culture and organisation), users (attributes and interactions between users) and the specific cardiovascular risk tool (characteristics, perceived role and effectiveness). While these findings bolster the understanding of implementation complexity, there exists limited research in the context of low and middle-income countries. Notwithstanding the need to direct resources in bridging this gap, it is also crucial that these efforts are in concert with providing high-quality evidence on the clinical effectiveness of using cardiovascular risk scoring to improve cardiovascular disease outcomes of mortality and morbidity. PROSPERO registration number: CRD42018092679.


Can the Application of Multi-Mode Adhesive be a Substitute to Silicatized/Silanized Y-TZP Ceramics?
This study evaluated the effectiveness of a multi-mode adhesive (SBU-Scotch Bond Universal/3M) as a substitute for silica coating and silane application on the bonding of zirconia ceramics to resin cement. One-hundred and twenty sintered zirconia ceramic blocks (5 x 5 x 5 mm) were obtained, finished by grounding with silicon carbide paper (#600, #800, #1000 and #1200) and randomly divided into 12 groups (n=10) in accordance with the factors "surface treatment" (ScSi - silicatization + silanization; ScSBU - silicatization + SBU; SBU - SBU without photoactivation and SBUp - SBU photoactivated) and "ceramic" (Lava / 3M ESPE, Ceramill Zirconia / Amann Girrbach and Zirkonzahn / Zirkonzahn). Dual resin cement cylinders (RelyX Ultimate/3M ESPE) were subsequently produced in the center of each block using a silicon matrix (Ø=2 mm, h=5 mm) and photoactivated for 40 s (1200 mW/cm2). The samples were stored for 30 days in distilled water (37ºC) and submitted to shear bond strength test (1 mm/min, 100 KgF). Data (MPa) were analyzed under ANOVA (2 levels) and Tukey test (5%). Complementary analyzes were also performed. ANOVA revealed that only the factor "surface treatment" was significant (p=0.0001). The ScSi treatment (14.28A) promoted statistically higher bond strength values than the other ScSBU (9.03B), SBU (8.47B) and SBUp (7.82B), which were similar to each other (Tukey). Failure analysis revealed that 100% of the failures were mixed. The silica coating followed by the silanization promoted higher bond strength values of resin cement and ceramic, regardless of the zirconia ceramic or SBU.


Revisiting the economic efficiencies of observation units.
Recent studies cast doubt about the economic efficiency of observation units (OUs). We aimed to reexamine the cost savings of OUs compared with inpatient care. Claims for 15,851 patients who were admitted to inpatient or OUs between January 2009 and December 2012 following emergency room (ER) visits for chest pain were retrospectively examined. The two groups were compared for total cost of episode, length of stay (LOS), and utilization rates of diagnostic procedures, including standard exercise and echocardiography stress tests, myocardial perfusion imaging (MPI), coronary computed tomography angiography (CCTA), and computed tomography (CT) chest scans. Total costs of care and LOS were adjusted for age, gender, risk scores, and comorbidities using quantile regression. More than 37% of the sample was admitted to inpatient units (n = 5,890) vs 62.7% to OUs (n = 9,961). Patients admitted to inpatient units had more comorbidities and longer LOS during their ER visit (median 1.5 adjusted days; 10th percentile = 1, 90th percentile = 3) vs. median 21 adjusted hours for OUs (20, 23). The adjusted median cost of OUs was $5,411 ($4,652, $7,157) vs. $6,946 for inpatient admission ($5,978, $18,683). The estimated adjusted cost saving of OUs was $1,535 (95% CI = $1,206, $1,411) compared with inpatient admission. About 37% of patients admitted to OUs stayed longer than 24 hours. Compared with patients admitted to inpatient units, patients in OUs also received more MPI (35.8% vs. 31.5%), CT scans (13.2% vs. 10.4%), standard exercise test (45.6% vs. 33.8%) and echocardiography stress test (8% vs. 3.4%). Despite the increased proportion of patients exceeding the 24-hour LOS and the increased utilization of advanced imaging procedures, OUs are still less costly compared with inpatient admission.


Endoscopic endonasal resection of the odontoid process: clinical outcomes in 34 adults.
OBJECTIVE Treatment of odontoid disease from a ventral corridor has consisted of a transoral approach. More recently, the endoscopic endonasal approach (EEA) has been used to access odontoid pathology. METHODS A retrospective review was conducted of patients who underwent an EEA for odontoid pathology from 2004 to 2013. During our analysis, the mean follow-up duration was 42.6 months (range 1-80 months). Patient outcomes, complications, and postoperative swallowing function were assessed either by clinic visit or phone contact. RESULTS Thirty-four patients underwent an EEA for symptomatic odontoid pathology. The most common pathology treated was basilar invagination (n = 17). Other pathologies included odontoid fractures, os odontoideum, and metastatic carcinoma. The mean patient age was 71.5 years. Thirty-one patients underwent a posterior fusion. All 34 patients experienced stability or improvement in symptoms and all had successful radiographic decompression. The overall complication rate was 76%. Nearly all of these complications were transient (86%) and the overall complication rate excluding mild transient dysphagia was only 44%. Twenty-one patients (62%) suffered from transient postoperative dysphagia: 15 cases were mild, transient subjective dysphagia (6 of whom had documented preoperative dysphagia), whereas 6 other patients required tube feedings for decreased oral intake, malnutrition, and dysphagia in the perioperative setting (5 of these patients had documented preoperative dysphagia). Sixteen patients had documented preoperative dysphagia and 6 of these had lower cranial nerve dysfunction. Postoperatively, 6 (37.5%) of 16 patients with preoperative dysphagia and 4 (67%) of 6 with lower cranial nerve dysfunction had significant dysphagia/respiratory complications. Eighteen patients had no documented preoperative dysphagia and only 2 had significant postoperative dysphagia/respiratory complications (11%). The rates of these complications in patients without preoperative dysphagia were lower than in those with any preoperative dysphagia (p = 0.07) and especially those with preexisting lower cranial neuropathies (p = 0.007). Dysphagia was also significantly more common in patients who underwent occipitocervical fixation (19/26, 73%) than in patients who underwent cervical fusion alone or no fusion (2/8, 25%; p = 0.02). All patients with perioperative dysphagia had improved at follow-up and all patients were tolerating oral diets. No patient suffered from velopalatal insufficiency. Two patients had intraoperative CSF leaks. One of these patients underwent a negative exploratory surgery for a questionable postoperative CSF leak. One patient developed infection in the resection bed requiring debridement and antibiotics. One patient died 8 days following surgery from an unknown cause. The 90-day perioperative mortality rate was 2.9%. CONCLUSIONS A completely EEA can be performed for compressive odontoid disease in all cases of neoplastic, degenerative, or invaginative atlantoaxial disease with satisfactory outcomes and low morbidity. Transient perioperative dysphagia and respiratory complications are common, usually as an exacerbation and reflection of underlying disease or occipitocervical fusion rather than the EEA, emphasizing the importance of avoiding transoral surgery.


Decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy.
The myotonic dystrophy mutation has recently been identified; however, the molecular mechanism of the disease is still unknown. The sequence of the myotonin-protein kinase gene was determined, and messenger RNA spliced forms were identified in various tissues. Antisera were developed for analytical studies. Quantitative reverse transcription-polymerase chain reaction and radioimmunoassay were used to demonstrate that decreased levels of the messenger RNA and protein expression are associated with the adult form of myotonic dystrophy.


Interventions for treating hyperemesis gravidarum.
Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for hospitalization during pregnancy. While a previous Cochrane review examined interventions for nausea and vomiting in pregnancy, there has not yet been a review examining the interventions for the more severe condition of hyperemesis gravidarum. To assess the effectiveness and safety, of all interventions for hyperemesis gravidarum in pregnancy up to 20 weeks' gestation. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (20 December 2015) and reference lists of retrieved studies. Randomized controlled trials of any intervention for hyperemesis gravidarum. Quasi-randomized trials and trials using a cross-over design were not eligible for inclusion.We excluded trials on nausea and vomiting of pregnancy that were not specifically studying the more severe condition of hyperemesis gravidarum. Two review authors independently reviewed the eligibility of trials, extracted data and evaluated the risk of bias. Data were checked for accuracy. Twenty-five trials (involving 2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. The comparisons covered a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various pharmaceutical interventions. The methodological quality of included studies was mixed. For selected important comparisons and outcomes, we graded the quality of the evidence and created 'Summary of findings' tables. For most outcomes the evidence was graded as low or very low quality mainly due to the imprecision of effect estimates. Comparisons included in the 'Summary of findings' tables are described below, the remaining comparisons are described in detail in the main text.No primary outcome data were available when acupuncture was compared with placebo, There was no clear evidence of differences between groups for anxiodepressive symptoms (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.40; one study, 36 women, very low-quality evidence), spontaneous abortion (RR 0.48, 95% CI 0.05 to 5.03; one study, 57 women, low-quality evidence), preterm birth (RR 0.12, 95% CI 0.01 to 2.26; one study, 36 women, low-quality evidence), or perinatal death (RR 0.57, 95% CI 0.04 to 8.30; one study, 36 women, low-quality evidence).There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (RR 1.40, 95% CI 0.79 to 2.49 and RR 1.51, 95% CI 0.92 to 2.48, respectively; very low-quality evidence).In a study with 92 participants, women taking vitamin B6 had a slightly longer hospital stay compared with placebo (mean difference (MD) 0.80 days, 95% CI 0.08 to 1.52, moderate-quality evidence). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40 to 1.40, low-quality evidence) or side effects.A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15 to 3.55, and MD -0.10, 95% CI -1.63 to 1.43; one study, 83 women, respectively, very low-quality evidence). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23 to 4.69, and RR 2.38, 95% CI 1.10 to 5.11, respectively; moderate-quality evidence). There were no clear differences between groups for other side effects.In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (RR 0.70, 95% CI 0.56 to 0.87, RR 0.48, 95% CI 0.34 to 0.69, and RR 0.31, 95% CI 0.11 to 0.90, respectively, moderate-quality evidence). There were no clear differences between groups for other important outcomes including quality of life and other side effects.In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (MD 0.00, 95% CI -1.39 to 1.39, very low-quality evidence), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00 to 0.94, low-quality evidence) .Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70 to 0.10; very low-quality evidence), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50 to 0.94; four studies, 269 women). For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, there was insufficient evidence to identify differences between groups (very low-quality evidence for all outcomes). In other single studies there were no clear differences between groups for preterm birth or side effects (very low-quality evidence).For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00 to 1.28;one study, 40 women).In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 hours (RR 2.00, 95% CI 1.08 to 3.72; low-quality evidence), but not at 17 days (RR 0.81, 95% CI 0.58 to 1.15, very low-quality evidence). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth. On the basis of this review, there is little high-quality and consistent evidence supporting any one intervention, which should be taken into account when making management decisions. There was also very limited reporting on the economic impact of hyperemesis gravidarum and the impact that interventions may have.The limitations in interpreting the results of the included studies highlights the importance of consistency in the definition of hyperemesis gravidarum, the use of validated outcome measures, and the need for larger placebo-controlled trials.


Chemical Dopant Engineering in Hole Transport Layers for Efficient Perovskite Solar Cells: Insight into the Interfacial Recombination.
Chemical doping of organic semiconductors has been recognized as an effective way to enhance the electrical conductivity. In perovskite solar cells (PSCs), various types of dopants have been developed for organic hole transport materials (HTMs); however, the knowledge of the basic requirements for being efficient dopants as well as the comprehensive roles of the dopants in PSCs has not been clearly revealed. Here, three copper-based complexes with controlled redox activities are applied as dopants in PSCs, and it is found that the oxidative reactivity of dopants presents substantial impacts on conductivity, charge dynamics, and solar cell performance. A significant improvement of open-circuit voltage ( Voc) by more than 100 mV and an increase of power conversion efficiency from 13.2 to 19.3% have been achieved by tuning the doping level of the HTM. The observed large variation of Voc for three dopants reveals their different recombination kinetics at the perovskite/HTM interfaces and suggests a model of an interfacial recombination mechanism. We also suggest that the dopants in HTMs can also affect the charge recombination kinetics as well as the solar cell performance. Based on these findings, a strategy is proposed to physically passivate the electron-hole recombination by inserting an ultrathin Al2O3 insulating layer between the perovskite and the HTM. This strategy contributes a significant enhancement of the power conversion efficiency and environmental stability, indicating that dopant engineering is one crucial way to further improve the performance of PSCs.


[Sulphureous mud-bath therapy and changes in blood pressure: observational investigation].
The chronic arthropathies currently appear to be a major cause of disability with a negative impact on quality of life and health care spending. The mud-bath therapy is a spa treatment that induces benefic effects in chronic rheumatic diseases. It has long been debated on the assumption that the mud-bath spa therapy could have adverse cardiovascular effects which often induce caution and even a contraindication to the use of this treatment in chronic arthropathies associated with cardiovascular alterations such as hypertension. The aim of this observational study was to investigate, in arthrorheumatic subjects, the effects of sulphureous mud-bath cycle on blood pressure and the possible appearance of adverse drug reaction. 169 patients, with age range 42-86 years, suffering by chronic arthropathies were treated with sulphureous mud-bath therapy for 2 weeks. According to the arterial pressure values, measured before the spa treatment, the patients considered were divided in three groups: with normal blood pressure (NOR group); with high blood pressure, after, the latter group was divided in IPET (patients in treatment with antihypertensive drugs) and IPENT (patients not in antihypertensive therapy). The arterial pressure values, maximum and minimum, expressed in mmHg, were detected in the first (T1) - sixth (T6) and twelfth (T12) day of spa treatment. The media arterial pressure values collected before and after T1, before and after T6, before and after T12 , before T1 and after T12 were compared. The data, presented as mean±SD, were compared with the paired Student t test. A p value ≤0.05 was considered significant. The comparison between the mean values detected in pre and post T1, pre and post T6, pre and post T12 have showed that sulphureous mud-bath therapy induced a significant (p<0.05) reduction of arterial blood pressure values in patients suffering of chronic arthropathies with high blood pressure in antihypertensive therapy or not (IPET and IPENT groups); while in patients with normal blood pressure (NOR group) were observed modest reduction at the limit of statistical significance. Similarly, the comparison between the data detected at the end of sulphureous mud-bath therapy (post-T12) vs baseline (pre-T1) have demonstrated: in IPET and IPENT groups a significant (p<0,01) decrease of arterial blood pressure values; in NOR group very small decrease, this reduction is significant (p<0.05) only for maximum arterial pressure value. Were not observed adverse drug reaction. The results of our study, in according with the few data in the literature, evidenced that is possible include the sulphureous mud-bath therapy in interdisciplinary therapeutic p rotocol of patients suffering of chronic arthropathies and arterial hypertension.


Exercise in patients with chronic obstructive pulmonary disease.
Patients with chronic obstructive pulmonary disease (COPD) may incur exercise limitation by any one or combination of disturbances in breathing mechanics, oxygen transport, respiratory muscle metabolism or respiratory regulation and sensation. In spite of the increased ventilation demand/capacity ratio in these patients, the relationship between breathing mechanics, respiratory muscle fatigue, the adequacy of alveolar ventilation and the development of exertional dyspnoea is neither clearly defined nor predictable from data obtained with the patient at rest. The issue of oxygen transport during exercise has been complicated by confusion between arterial hypoxia and inadequate volume of oxygen transported to the tissues, which frequently may differ qualitatively and quantitatively. The cardiac output response to exercise in patients with COPD is therefore critical in determining oxygen transport. This response is also impossible to predict from resting lung mechanics, pulmonary arterial blood pressure, arterial oxygen tension or clinical disease profile. Without exercise testing, which includes measurement of all the variables mentioned, it is impossible to define clearly the cause of exercise-induced symptoms in patients with COPD. Exercise training with and without supplemental oxygen has been shown to improve exercise tolerance in these patients, but the precise mechanism of this improvement remains obscure.


Infantile mitochondrial disorders.
Mitochondrial disorders encompass any medical specialty and affect patients at any age. Likewise, the spectrum of clinical and genetic signatures of these disorders is ample, making a precise diagnosis difficult. We will report some of the major clinical phenotypes observed in infancy, their underlining molecular features, and will propose an approach to reach a more complete diagnosis.


Inherited phosphofructokinase deficiency in dogs with hyperventilation-induced hemolysis: increased in vitro and in vivo alkaline fragility of erythrocytes.
Two male English springer spaniel dogs with a chronic hemolytic anemia and sporadic hemolytic crises, historically related to "stress" situations, were studied. Although canine erythrocytes are in general known to be more alkaline fragile, erythrocytes from both patients began to lyse earlier, at significantly lower pH values (near pH 7.4 at 37 degrees C), than erythrocytes from control dogs. Hyperventilation induced by 30 minutes of exercise, placement in a 39 degrees C water bath, or intravenous doxapram increased venous blood pH in dog 1 and control dogs, but transient hemoglobinemia, hemoglobinuria, and severe bilirubinuria occurred only in the studied patient. The erythrocyte phosphofructokinase (PFK) activity was severely decreased in both dogs (10% of controls). The erythrocyte 2,3-diphosphoglycerate content was markedly reduced and the cell chloride content was consequently increased. This change in cell chloride content is related to an increase in the erythrocyte pH, which may partially explain the pathogenesis of hemolysis in canine PFK deficiency. Thus, these studies demonstrate a presumably inherited erythrocyte PFK deficiency in English springer spaniels, which causes an increased in vitro and in vivo erythrocyte alkaline fragility. Dogs with PFK deficiency and inducible hemolytic crises may become a valuable genetic animal model in which to study the pathophysiology of hemolysis.


Transcriptome-derived evidence supports recent polyploidization and a major phylogeographic division in Trithuria submersa (Hydatellaceae, Nymphaeales).
Relatively little is known about species-level genetic diversity in flowering plants outside the eudicots and monocots, and it is often unclear how to interpret genetic patterns in lineages with whole-genome duplications. We addressed these issues in a polyploid representative of Hydatellaceae, part of the water-lily order Nymphaeales. We examined a transcriptome of Trithuria submersa for evidence of recent whole-genome duplication, and applied transcriptome-derived microsatellite (expressed-sequence tag simple-sequence repeat (EST-SSR)) primers to survey genetic variation in populations across its range in mainland Australia. A transcriptome-based Ks plot revealed at least one recent polyploidization event, consistent with fixed heterozygous genotypes representing underlying sets of homeologous loci. A strong genetic division coincides with a trans-Nullarbor biogeographic boundary. Patterns of 'allelic' variation (no more than two variants per EST-SSR genotype) and recently published chromosomal evidence are consistent with the predicted polyploidization event and substantial homozygosity underlying fixed heterozygote SSR genotypes, which in turn reflect a selfing mating system. The Nullarbor Plain is a barrier to gene flow between two deep lineages of T. submersa that may represent cryptic species. The markers developed here should also be useful for further disentangling species relationships, and provide a first step towards future genomic studies in Trithuria.


Co-operative membrane disruption between cell-penetrating peptide and cargo: implications for the therapeutic use of the Bcl-2 converter peptide D-NuBCP-9-r8.
Delivering apoptosis inducing peptides to cells is an emerging area in cancer and molecular therapeutics. Here, we have identified an alternative mechanism of action for the proapoptotic chimeric peptide D-NuBCP-9-r8. Integral to D-NuBCP-9-r8 is the Nur-77-derived D-isoform sequence fsrslhsll that targets Bcl-2, and the cell-penetrating peptide (CPP) octaarginine (r8) that is required for intracellular delivery. We find that the N-terminal phenylalanine of fsrslhsll acts in synergy with the cell-penetrating moiety to enhance peptide uptake at low nontoxic levels and cause rapid membrane blebbing and cell necrosis at higher (IC(50)) concentrations. These effects were not observed when a single phenylalanine-alanine mutation was introduced at the N-terminus of D-NuBCP-9-r8. Using primary samples from chronic lymphocytic leukemia (CLL) patients and cancer cell lines, we show that NuBCP-9-r8 induced toxicity, via membrane disruption, is independent of Bcl-2 expression. Overall, this study demonstrates a new mechanism of action for this peptide and cautions its use as a highly specific entity for targeting Bcl-2. For delivery of therapeutic peptides the work emphasizes that key amino acids in cargo, located several residues away from the cell-penetrating sequence, can significantly influence their cellular uptake and mode of action.


Genome of the human hookworm Necator americanus.
The hookworm Necator americanus is the predominant soil-transmitted human parasite. Adult worms feed on blood in the small intestine, causing iron-deficiency anemia, malnutrition, growth and development stunting in children, and severe morbidity and mortality during pregnancy in women. We report sequencing and assembly of the N. americanus genome (244 Mb, 19,151 genes). Characterization of this first hookworm genome sequence identified genes orchestrating the hookworm's invasion of the human host, genes involved in blood feeding and development, and genes encoding proteins that represent new potential drug targets against hookworms. N. americanus has undergone a considerable and unique expansion of immunomodulator proteins, some of which we highlight as potential treatments against inflammatory diseases. We also used a protein microarray to demonstrate a postgenomic application of the hookworm genome sequence. This genome provides an invaluable resource to boost ongoing efforts toward fundamental and applied postgenomic research, including the development of new methods to control hookworm and human immunological diseases.


Caries correlates strongly to salivary levels of matrix metalloproteinase-8.
The caries process in dentin involves the degradation of both mineral and organic matrix. The demineralization has been demonstrated to be caused by bacterial acids. However, the collagen degradation is considered to be initiated by endogenous proteolytic enzymes, mainly collagenolytic matrix metalloproteinases (MMPs). This paper aims to relate salivary MMP-8 (or salivary collagenase-2) and tissue inhibitor of MMP (TIMP-1) levels to manifest caries in a large number of subjects. A random sample of 451 adults (aged 18-87 years) living in the south of Sweden was included in this study. Standard clinical examinations were performed, and stimulated saliva was collected and analyzed for concentrations of MMP-8, TIMP-1 and total protein, using an immunofluorometric assay, an enzyme-linked immunosorbent assay and the Bradford assay, respectively. Salivary numbers of mutans streptococci and lactobacilli were determined using a chair-side kit. Subjects with manifest caries lesions presented with elevated levels of MMP-8 (p < 0.001) as well as total protein, MMP-8/TIMP-1 ratio, bleeding on probing and plaque index (p = 0.05) compared with subjects without manifest caries. Multiple linear regression analysis with caries as the dependent variable revealed MMP-8 as the only significant explanatory variable (p < 0.001). TIMP-1 was not significant in any case. Using MMP-8 as the dependent variable revealed total protein concentration, caries lesions (p ≤ 0.001) and salivary secretion rate (p = 0.05) as explanatory variables. In conclusion, our data reveal that subjects with manifest caries lesions have elevated levels of salivary MMP-8 relative to subjects with no caries lesions.


Exome sequencing extends the phenotypic spectrum for ABHD12 mutations: from syndromic to nonsyndromic retinal degeneration.
To identify the genetic causes underlying autosomal recessive retinitis pigmentosa (arRP) and to describe the associated phenotype. Case series. Three hundred forty-seven unrelated families affected by arRP and 33 unrelated families affected by retinitis pigmentosa (RP) plus noncongenital and progressive hearing loss, ataxia, or both, respectively. A whole exome sequencing (WES) analysis was performed in 2 families segregating arRP. A mutational screening was performed in 378 additional unrelated families for the exon-intron boundaries of the ABHD12 gene. To establish a genotype-phenotype correlation, individuals who were homozygous or compound heterozygotes of mutations in ABHD12 underwent exhaustive clinical examinations by ophthalmologists, neurologists, and otologists. DNA sequence variants, best-corrected visual acuity, visual field assessments, electroretinogram responses, magnetic resonance imaging, and audiography. After a WES analysis, we identified 4 new mutations (p.Arg107Glufs*8, p.Trp159*, p.Arg186Pro, and p.Thr202Ile) in ABHD12 in 2 families (RP-1292 and W08-1833) previously diagnosed with nonsyndromic arRP, which cosegregated with the disease among the family members. Another homozygous mutation (p.His372Gln) was detected in 1 affected individual (RP-1487) from a cohort of 378 unrelated arRP and syndromic RP patients. After exhaustive clinical examinations by neurologists and otologists, the 4 affected members of the RP-1292 had no polyneuropathy or ataxia, and the sensorineural hearing loss and cataract were attributed to age or the normal course of the RP, whereas the affected members of the families W08-1833 and RP-1487 showed clearly symptoms associated with polyneuropathy, hearing loss, cerebellar ataxia, RP, and early-onset cataract (PHARC) syndrome. Null mutations in the ABHD12 gene lead to PHARC syndrome, a neurodegenerative disease including polyneuropathy, hearing loss, cerebellar ataxia, RP, and early-onset cataract. Our study allowed us to report 5 new mutations in ABHD12. This is the first time missense mutations have been described for this gene. Furthermore, these findings are expanding the spectrum of phenotypes associated with ABHD12 mutations ranging from PHARC syndrome to a nonsyndromic form of retinal degeneration.


Factors influencing overweight children's commencement of and continuation in a resistance training program.
In light of the child overweight and obesity problem in Australia, resistance training programs have been trialled as an innovative way of assisting children increase lean body mass and reduce body fat. The purpose of this study was to investigate the factors influencing overweight children's participation in a resistance training trial program. Parent-child pairs who participated in the trial program were invited to take part in a follow-up individual interview to discuss their program experiences. In total, 22 semi-structured interviews were conducted with 11 parent-child pairs. The factors found to be most relevant to program commencement among parents were a desire for their child to lose weight and gain confidence, the proximity of the venue, and no cost for participation. For children, the most relevant factors were the opportunity to build strength and improve fitness and having supportive parents who facilitated program initiation. The factors most relevant to continuation for parents were the quality of the program management, being able to stay for the sessions, the child's improved weight status, coordination, and confidence, and no cost for participation. Weight loss and improved confidence were also motivators for continuation among the children, along with pleasant social interaction with peers and trainers and ongoing parental support. Different factors variably influence program commencement and program continuation in both parents and children. This has important implications for future interventions that aim to successfully recruit and retain intervention participants.


Determination of the role of target tissue metabolism in lung carcinogenesis using conditional cytochrome P450 reductase-null mice.
Critical to mechanisms of chemical carcinogenesis and the design of chemopreventive strategies is whether procarcinogen bioactivation in an extrahepatic target tissue (e.g., the lung) is essential for tumor formation. This study aims to develop a mouse model capable of revealing the role of pulmonary microsomal cytochrome P450 (P450)-mediated metabolic activation in xenobiotic-induced lung cancer. A novel triple transgenic mouse model, with the NADPH-P450 reductase (Cpr) gene deleted in a lung-specific and doxycycline-inducible fashion (lung-Cpr-null), was generated. CPR, the obligate electron donor for microsomal P450 enzymes, is essential for the bioactivation of many procarcinogens. The lung-Cpr-null mouse was studied to resolve whether pulmonary P450 plays a major role in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer by producing carcinogenic metabolites in the target tissue. A liver-Cpr-null mouse was also studied to test whether hepatic P450 contributes predominantly to systemic clearance of NNK, thereby decreasing NNK-induced lung cancer. The numbers of NNK-induced lung tumors were reduced in the lung-Cpr-null mice but were increased in the liver-Cpr-null mice, relative to wild-type control mice. Decreased lung tumor multiplicity in the lung-Cpr-null mice correlated with reduced lung O6-methylguanine adduct levels, without decreases in NNK bioavailability, consistent with decreased NNK bioactivation in the lung. Moreover, lung tumors in lung-Cpr-null mice were positive for CPR expression, indicating that the tumors did not originate from Cpr-null cells. Thus, we have confirmed the essential role of pulmonary P450-mediated metabolic activation in NNK-induced lung cancer, and our mouse models should be applicable to studies on other procarcinogens that require P450-mediated metabolic activation.


Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support.
Endogenous cytokines are thought to mediate numerous biologic processes and may account for some adverse effects experienced following the administration of recombinant proteins. This study describes the pattern of endogenous cytokine exposure following high-dose chemotherapy. Blood concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor (M-CSF), and erythropoietin (EPO) were measured by enzyme-linked immunosorbent assay (ELISA) methods in 68 patients receiving the same ablative chemotherapy regimen (cyclophosphamide, cisplatin, carmustine). Patients were grouped according to cellular support (autologous bone marrow [BM] CSF-primed peripheral blood progenitor cells [PBPCs]) and prescribed growth factor (recombinant human granulocyte or granulocyte-macrophage colony-stimulating factor [rHuG-CSF or rHuGM-CSF]). Leukocyte reconstitution was most accelerated in the groups treated with PBPCs and rHuG-CSF. IL-6, M-CSF, and TNF-alpha concentrations were higher in the groups treated with rHuGM-CSF and without PBPCs. Maximal endogenous cytokine concentrations occurred approximately 12 days after BM reinfusion. High concentrations of EPO occurred in patients experiencing significant hypotension despite routine transfusions for hematocrit < 42%. High M-CSF and IL-6 levels were associated with increased platelet transfusion requirements. Concentrations of all four cytokines were significantly higher in patients experiencing renal or hepatic toxicity, with elevations occurring in a predictable sequence and M-CSF elevations occurring first. This report shows that endogenous cytokine concentrations may be influenced by either cellular or CSF support and are associated with differences in platelet reconstitution and organ toxicity.


Microstructural white matter abnormalities in hypothyroidism evaluation with diffusion tensor imaging tract-based spatial statistical analysis.
Hypothyroidism is presented in a wide range from neuropsychiatric problems including depression, memory and cognitive disorders to poor motor coordination. Against the background of morphologic, functional and molecular changes on the white and grey matter of the brain, we aimed to investigate the effects of hypothyroidism on white matter (WM) integrity using tract-based spatial statistics (TBSS). Eighteen patients with hyperthyroidism and 14 age-sex-matched healthy control subjects were included in this study. TBSS was used in the diffusion tensor imaging study for whole-brain voxel wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) of WM. When compared to the control group, the whole brain TBSS revealed extensive reductions of FA in the supratentorial WM including corticospinal tract, posterior limb of the internal capsule (PLIC), uncinate fasciculus, inferior longitudinal fasciculus (p < 0.005). The ROI analyses showed RD increment of superior longitudinal fasciculus, AD decrement of cingulum (CIN), external capsule, PLIC and corpus callosum (CC) in patients with hypothyroidism (p < 0.005). Autoimmune and non-autoimmune hypothyroidism patient subgroups showed a significant difference in terms of hippocampus FA, CIN MD, CC MD, CC AD, CIN RD, SLF RD, CC RD (p < 0.005). CIN FA values showed a negative correlation with the Beck Depression Inventory (p = 0.007, r = - 852). These preliminary results of TBSS analyses represented FA and AD decrement, and RD increment in several WM tracts and indicates the demyelination process underlying pathophysiology of clinical aspects of hypothyroidism.


Characteristics and functional relevance of apolipoprotein-A1 and cholesterol binding in mammary gland tissues and epithelial cells.
Cholesterol in milk is derived from the circulating blood through a complex transport process involving the mammary alveolar epithelium. Details of the mechanisms involved in this transfer are unclear. Apolipoprotein-AI (apoA-I) is an acceptor of cellular cholesterol effluxed by the ATP-binding cassette (ABC) transporter A1 (ABCA1). We aimed to 1) determine the binding characteristics of (125)I-apoA-I and (3)H-cholesterol to enriched plasma membrane vesicles (EPM) isolated from lactating and non-lactating bovine mammary glands (MG), 2) optimize the components of an in vitro model describing cellular (3)H-cholesterol efflux in primary bovine mammary epithelial cells (MeBo), and 3) assess the vectorial cholesterol transport in MeBo using Transwell(®) plates. The amounts of isolated EPM and the maximal binding capacity of (125)I-apoA-I to EPM differed depending on the MG's physiological state, while the kinetics of (3)H-cholesterol and (125)I-apoA-I binding were similar. (3)H-cholesterol incorporated maximally to EPM after 25±9 min. The time to achieve the half-maximum binding of (125)I-apoA-I at equilibrium was 3.3±0.6 min. The dissociation constant (KD) of (125)I-apoA-I ranged between 40-74 nmol/L. Cholesterol loading to EPM increased both cholesterol content and (125)I-apoA-I binding. The ABCA1 inhibitor Probucol displaced (125)I-apoA-I binding to EPM and reduced (3)H-cholesterol efflux in MeBo. Time-dependent (3)H-cholesterol uptake and efflux showed inverse patterns. The defined binding characteristics of cholesterol and apoA-I served to establish an efficient and significantly shorter cholesterol efflux protocol that had been used in MeBo. The application of this protocol in Transwell(®) plates with the upper chamber mimicking the apical (milk-facing) and the bottom chamber corresponding to the basolateral (blood-facing) side of cells showed that the degree of (3)H-cholesterol efflux in MeBo differed significantly between the apical and basolateral aspects. Our findings support the importance of the apoA-I/ABCA1 pathway in MG cholesterol transport and suggest its role in influencing milk composition and directing cholesterol back into the bloodstream.


Integral imaging based 3D display of holographic data.
We propose a method and present applications of this method that converts a diffraction pattern into an elemental image set in order to display them on an integral imaging based display setup. We generate elemental images based on diffraction calculations as an alternative to commonly used ray tracing methods. Ray tracing methods do not accommodate the interference and diffraction phenomena. Our proposed method enables us to obtain elemental images from a holographic recording of a 3D object/scene. The diffraction pattern can be either numerically generated data or digitally acquired optical data. The method shows the connection between a hologram (diffraction pattern) and an elemental image set of the same 3D object. We showed three examples, one of which is the digitally captured optical diffraction tomography data of an epithelium cell. We obtained optical reconstructions with our integral imaging display setup where we used a digital lenslet array. We also obtained numerical reconstructions, again by using the diffraction calculations, for comparison. The digital and optical reconstruction results are in good agreement.


Trauma in the developing world: the jamaican experience.
Trauma remains a challenging burden on the often under-funded healthcare systems of developing countries. Ten-year data from the Jamaica Trauma Registry show that trauma accounts for 20% of surgical admissions, with close to 50% being intentional and with a 5% mortality. There is a good opportunity for various preventive programmes to be instituted to reduce the burden of this disease.


Grating and plaid masks indicate linear summation in a contrast gain pool.
In human vision, the response to luminance contrast at each small region in the image is controlled by a more global process where suppressive signals are pooled over spatial frequency and orientation bands. But what rules govern summation among stimulus components within the suppressive pool? We addressed this question by extending a pedestal plus pattern mask paradigm to use a stimulus with up to three mask components: a vertical 1 c/deg pedestal, plus pattern masks made from either a grating (orientation = -45 degrees ) or a plaid (orientation = +/-45 degrees ), with component spatial frequency of 3 c/deg. The overall contrast of both types of pattern mask was fixed at 20% (i.e., plaid component contrasts were 10%). We found that both of these masks transformed conventional dipper functions (threshold vs. pedestal contrast with no pattern mask) in exactly the same way: The dipper region was raised and shifted to the right, but the dipper handles superimposed. This equivalence of the two pattern masks indicates that contrast summation between the plaid components was perfectly linear prior to the masking stage. Furthermore, the pattern masks did not drive the detecting mechanism above its detection threshold because they did not abolish facilitation by the pedestal (Foley, 1994). Therefore, the pattern masking could not be attributed to within-channel masking, suggesting that linear summation of contrast signals takes place within a suppressive contrast gain pool. We present a quantitative model of the effects and discuss the implications for neurophysiological models of the process.


The Experience Elicited by Hallucinogens Presents the Highest Similarity to Dreaming within a Large Database of Psychoactive Substance Reports.
Ever since the modern rediscovery of psychedelic substances by Western society, several authors have independently proposed that their effects bear a high resemblance to the dreams and dreamlike experiences occurring naturally during the sleep-wake cycle. Recent studies in humans have provided neurophysiological evidence supporting this hypothesis. However, a rigorous comparative analysis of the phenomenology ("what it feels like" to experience these states) is currently lacking. We investigated the semantic similarity between a large number of subjective reports of psychoactive substances and reports of high/low lucidity dreams, and found that the highest-ranking substance in terms of the similarity to high lucidity dreams was the serotonergic psychedelic lysergic acid diethylamide (LSD), whereas the highest-ranking in terms of the similarity to dreams of low lucidity were plants of the Datura genus, rich in deliriant tropane alkaloids. Conversely, sedatives, stimulants, antipsychotics, and antidepressants comprised most of the lowest-ranking substances. An analysis of the most frequent words in the subjective reports of dreams and hallucinogens revealed that terms associated with perception ("see," "visual," "face," "reality," "color"), emotion ("fear"), setting ("outside," "inside," "street," "front," "behind") and relatives ("mom," "dad," "brother," "parent," "family") were the most prevalent across both experiences. In summary, we applied novel quantitative analyses to a large volume of empirical data to confirm the hypothesis that, among all psychoactive substances, hallucinogen drugs elicit experiences with the highest semantic similarity to those of dreams. Our results and the associated methodological developments open the way to study the comparative phenomenology of different altered states of consciousness and its relationship with non-invasive measurements of brain physiology.


Environmental and Sensor Integration Influences on Temperature Measurements by Rotary-Wing Unmanned Aircraft Systems.
Obtaining thermodynamic measurements using rotary-wing unmanned aircraft systems (rwUAS) requires several considerations for mitigating biases from the aircraft and its environment. In this study, we focus on how the method of temperature sensor integration can impact the quality of its measurements. To minimize non-environmental heat sources and prevent any contamination coming from the rwUAS body, two configurations with different sensor placements are proposed for comparison. The first configuration consists of a custom quadcopter with temperature and humidity sensors placed below the propellers for aspiration. The second configuration incorporates the same quadcopter design with sensors instead shielded inside of an L-duct and aspirated by a ducted fan. Additionally, an autopilot algorithm was developed for these platforms to face them into the wind during flight for kinematic wind estimations. This study will utilize in situ rwUAS observations validated against tower-mounted reference instruments to examine how measurements are influenced both by the different configurations as well as the ambient environment. Results indicate that both methods of integration are valid but the below-propeller configuration is more susceptible to errors from solar radiation and heat from the body of the rwUAS.