Polycystic ovary syndrome: Current scenario and future insights.
Polycystic ovary syndrome (PCOS) prevails in approximately 33% of females of reproductive age globally. Although the root cause of the disease is unknown, attempts are made to clinically manage the disturbed hormone levels and symptoms arising due to hyperandrogenism, a hallmark of PCOS. This review presents detailed insights on the etiology, risk factors, current treatment strategies, and challenges therein. Medicinal agents currently in clinical trials and those in the development pipeline are emphasized. The significance of the inclusion of herbal supplements in PCOS and the benefits of improved lifestyle are also explained. Last, emerging therapeutic targets for treating PCOS are elaborated. The present review will assist the research fraternity working in the concerned domain to access significant knowledge associated with PCOS.


Understanding sociality and behavior change associated with a nesting event in a captive flock of great white pelicans.
Zoo-housed pelicans are commonplace, but their breeding record is poor and little research is published on the activity patterns, as potential predictors of nesting, of captive flocks. Existing literature shows that comparative research can provide useful information for husbandry and conservation planning for pelican populations. The opportunity arose to investigate the time-activity budget and social network of a breeding flock of captive great white pelicans. Three chicks were hatched in June and July 2016 and one in March 2017. Data on state behaviors, space use, and association preferences were collected around these nesting events, from October 2016 to February 2017 and July to October 2017. Results suggest that pre-nesting periods were associated with heightened flock-wide vigilance, suggesting that vigilance may be a precursor for courtship or nesting activity. Social network analysis revealed nonrandom associations between birds and a social structure across the flock, in which subadults seemed to associate more with each other than with adult birds. A limited visitor effect was noted; whilst no overall behavior change was apparent with different numbers of visitors, pelicans did widen their enclosure usage with increased visitor presence. These data are relevant to those attempting to breed this pelican, who wish to know more about the daily behavior patterns of this species across the season and physiological state, and who wish to understand pelican social structure, which is useful to the planning and implementation of bird moves or changes to the social environment of the flock. Further extending such research to include uninterrupted observation over a successful breeding event is recommended.


Peripheral nerve injuries from intramuscular injection of drugs.
17 patients who were treated at the University of Nigeria Teaching Hospital for peripheral nerve paralysis resulting from intramuscular injection of drugs are analyzed. Ten of them were below the age of 5 years. Sciatic nerve was affected in 16 patients and only one patient had median nerve paralysis. Penicillin, ampicillin, tetracycline, paraldehyde and optalgin were some of the offending drugs. The prognosis was poor as only three patients achieved a partial recovery of function in the paralyzed nerves. With determination and public education, this iatrogenic tragedy could be eradicated.


A new local multiscale Fourier analysis for medical imaging.
The Stockwell transform (ST), recently developed for geophysics, combines features of the Fourier, Gabor and wavelet transforms; it reveals frequency variation over time or space. This valuable information is obtained by Fourier analysis of a small segment of a signal at a time. Localization of the Fourier spectrum is achieved by filtering the signal with frequency-dependent Gaussian scaling windows. This multi-scale time-frequency analysis provides information about which frequencies occur and more importantly when they occur. Furthermore, the Stockwell domain can be directly inferred from the Fourier domain and vice versa. These features make the ST a potentially effective tool to visualize, analyze, and process medical imaging data. The ST has proven useful in noise reduction and tissue texture analysis. Herein, we focus on the theory and effectiveness of the ST for medical imaging. Its effectiveness and comparison with other linear time-frequency transforms, such as the Gabor and wavelet transforms, are discussed and demonstrated using functional magnetic resonance imaging data.


Quantifying cellular protrusion in alginate capsules with covalently crosslinked shells.
This work describes viability and distribution of INS-1E beta cells in shell-crosslinked alginate capsules, focussing on cells located near the capsule surface. Capsules were formed by air-shearing alginate suspensions of INS-1E cells into a gelling bath, and coating with poly-l-lysine (PLL) and 50% hydrolysed poly(methylvinylether-alt-maleic anhydride) to form crosslinked networks reinforcing the capsule surfaces. The percentage of cells at the capsule surface were determined using 2D and 3D confocal colocalization mapping. Encapsulated INS-1E cells showed high cell viability and progressive cell clustering out to six weeks. About 30% of cells were initially colocated with the 20 micrometer thick alginate-PLL-PMM50 shell, with 7% of cells protruded at the capsule surfaces, both reflecting random cell distributions. Protruding cells may cause cell-based immune responses, weaken capsules, and potentially result in cell escape from the capsules. The data shown indicate that reinforcing capsules with crosslinked shells may assist in preventing cell exposure and escape.


Effect of a somatostatin analogue on trophic hormone levels in acromegalic patients with elevated hGH after adenomectomy and treatment with bromocriptine.
Five female acromegalic patients who had undergone surgical adenomectomy, but still had elevated hGH serum levels, were treated with bromocriptine, 5-15 mg daily, for at least 4 months without a satisfactory response. In an attempt to lower serum hGH levels, p-NH2-Phe4-D-Trp8-somatostatin was administered, 100 micrograms as an i.v. bolus, followed by infusion of 250 micrograms over a 4 hour period. The analogue decreased hGH levels by about 50% in 3 out of 5 patients, both during bromocriptine treatment and also in its absence. Of the remaining two patients, one showed a decrease in hGH levels in response to the analogue only during bromocriptine treatment and the other only without it. Saline infusion after bromocriptine administration did not induce a decrease in hGH levels in three of these patients. Somatostatin analogue caused a fall in serum insulin levels in all but one patient, who had diabetes mellitus and in whom serum insulin was undetectable. Both hGH and insulin levels showed a significant rebound after infusion of the analogue, but returned to basal levels within 24 hours. Prolactin did not change during the analogue infusion in 4 patients with normal PRL levels. However, in one patient in whom prolactin and hGH levels were elevated during bromocriptine treatment, the infusion of somatostatin analogue decreased both hormones. The analogue induced no changes in serum TSH, FSH and LH levels of any of the patients.


Pyroelectrically-driven chemical reactions described by a novel thermodynamic cycle.
Pyroelectrocatalysis is the conversion of thermal energy directly into chemical energy. On the background of renewable energies and the need for efficient industrial processes, the conversion of waste heat into hydrogen is of special relevance. Since the reported thermodynamic cycles for pyroelectric energy harvesting do not fit the conditions encountered in a reactive medium such as water appropriately, we describe a new thermodynamic charge-voltage-cycle characterised by fixed upper and lower potentials. These threshold potentials comprise the redox potential of the reaction of interest - here the hydrogen evolution reaction - as well as an overpotential mainly dictated by the temperature-induced bending of electronic bands in the pyroelectric semiconductor. Because polarisation changes below the threshold are useless for chemical reactions, material properties as well as process conditions have to be chosen accordingly. In particular the particle size along with the temperature difference are shown to determine the conversion efficiency.


Identification of a labile protein involved in the G1-to-S transition in Saccharomyces cerevisiae.
The biochemical nature of the start process that commits budding yeast to DNA synthesis is not known. Kinetic evidence has suggested recently that short-lived protein(s) may have to accumulate to a critical level before the cell cycle may progress towards DNA synthesis and cell division. We investigated by high-resolution two-dimensional electrophoresis whether, in a cdc25-1 mutant strain of Saccharomyces cerevisiae that had been blocked at the regulatory step called "start" by growth at a restrictive temperature, short-lived proteins are synthesized during the recovery of growth at a permissive temperature. Of the approximately equal to 500 proteins resolved by the two-dimensional electrophoresis, 6 were short-lived. Only one of them (Mr = 100,000, pI approximately equal to 4.8-5) appears to be specifically made during the G1-to-S transition at start. A regulatory role for cell cycle progression in yeast is suggested for this protein, p100.


Sedation and renal impairment in critically ill patients: a post hoc analysis of a randomized trial.
Not sedating critically ill patients reduces the time patients receive mechanical ventilation, decreases the time in the intensive care department and reduces the total hospital length of stay. We hypothesized that no sedation improves hemodynamic stability, decreases the need for vasoactive drugs, diminishes the need for extra fluids and lowers the risk of acute kidney injury. We performed an evaluation on the database from our previous trial of 140 patients randomized to either no sedation vs. sedation with a daily interruption of sedatives. A total of 113 patients were included in the previous statistical analysis. Ten patients had pre-existing renal impairments and were excluded. Data were collected from observational cards and blood samples. A total of 103 patients were included in this retrospective review. We registered an increased urine output in the group receiving no sedation compared to the sedated control group (1.15 ml/kg/hour (0.59 to 1.53) vs. 0.88 ml/kg/hour (0.052 to 1.26), P = 0.03). In addition we saw a decrease in the number of patients with renal impairment according to the RIFLE classification (indicating Risk of renal dysfunction; Injury to the kidney; Failure of kidney function, Loss of kidney function and End-stage kidney disease) in the group receiving no sedation compared to the sedated control group (25 (51%) vs. 41 (76%), P = 0.012). The difference in the two groups with respect to mean arterial blood pressure, fluid balance and use of vasoactive drugs was not significant. A no sedation strategy to patients undergoing mechanical ventilation increases the urine output and decreases the number of patients with renal impairments.


Olfactory attraction of the larval parasitoid, Hyposoter horticola, to plants infested with eggs of the host butterfly, Melitaea cinxia.
Parasitoids locate inconspicuous hosts in a heterogeneous habitat using plant volatiles, some of which are induced by the hosts. Hyposoter horticola Gravenhost (Hymenoptera: Ichneumonidae) is a parasitoid of the Glanville fritillary butterfly Melitaea cinxia L. (Lepidoptera: Nymphalidae). Melitaea cinxia lays eggs in clusters on leaves of Plantago lanceolata L. (Lamiales: Plantaginaceae) and Veronica spicata L. (Lamiales: Plantaginaceae). The parasitoid oviposits into host larvae that have not yet hatched from the egg. Thus, though H. horticola is a parasitoid of Melitaea cinxia larvae, it must find host eggs on plants that have not been fed on by the larvae. Using a Y-tube olfactometer, the response of H. horticola to odors of Melitaea cinxia and extracts of the attacked plant species were tested. Three week-old eggs (near hatching) were attractive to young H. horticola, but one week-old eggs were attractive only to old or experienced H. horticola. Melitaea cinxia larvae were not attractive. A water extract of P. lanceolata was attractive, but ethanol or hexane extracts were not. None of the extracts of V. spicata were attractive. Leaves of V. spicata were attractive only if harboring eggs, but P. lanceolata leaves with eggs were not. Free flying H. horticola in a large outdoor enclosure were presented with host and plant cues. As in the olfactometer, V. spicata was attractive only when eggs were on it, and P. lanceolata was somewhat attractive with or without eggs. This study shows for the first time that a parasitoid of larvae uses egg volatiles or oviposition-induced plant volatiles, to find host larvae, and that Melitaea cinxia eggs or traces of oviposition induce the production of these volatiles by the plant. Based on the results, and given the natural distribution of the plants and M. cinxia eggs, parasitism of Melitaea cinxia eggs on P. lanceolata would be expected to be low. Instead, under natural conditions, a fraction of the eggs in virtually all egg clusters are parasitized on both plant species. The mismatch between the experimental results and the natural pattern of host-parasitoid interactions is discussed in terms of the expected coupling foraging cues with foraging success.


Intestinal infarction associated with mesenteric vascular thrombotic disease in the horse.
Intestinal infarction associated with cranial mesenteric artery thrombosis, without strangulation obstruction of the intestine, was studied in 18 horses. Findings normally of value in evaluating horses with acute abdominal pain (heart rate, rectal palpation findings, gastric reflux) or classification of the degree of pain were not helpful in diagnosing the problem. Similarly, packed cell volume, plasma total protein, circulating white blood cell count, peritoneal white blood cell count, and peritoneal fluid total protein were not of value in predicting severity of the intestinal damage, location of infarction, or patient survival. In one half of the cases, peritoneal fluid color was of aid in distinguishing intestinal infarction from strangulation. Findings on gross dissection and limited histologic examination did not support the premise that thromboembolism was the major mechanism for production of infarction. In most of the horses, a thrombus or embolus was not found in the peripheral mesenteric vessels.


The effect of acute heat exposure on rat pituitary corticotroph activation: the role of vasopressin.
The increased ambient temperature affects the function of hypothalamic-pituitary-adrenal (HPA) axis. Since the correlation among vasopressin (VP), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses to various stressors have been long recognized, the aim of this study was to reveal the aforementioned hormones production and morphology of the pituitary gland after exposure to acute heat. Rats were exposed to high ambient temperature (38 °C) for 20 or 60 minutes. The circulating hormones were determined by an ELISA test or chemiluminescence's method. The results obtained show the elevation in ACTH and CORT secretion depending on the duration of heat exposure. The VP concentration increased only after prolonged exposure to heat (60 min). The pituitary morphology was examined by routine and fluorescent immunohistochemistry as well as electron microscopy. Observed changes in the anterior and posterior pituitary well corresponded to circulating hormones, regarding the volume density of ACTH-immunopositive cells, percentage of ACTH immunopositive area v. total area and number of VP-immunopositive containing varicose fibers per total area. Acute heat exposure also induced changes in shapes of ACTH-immunopositive cells. Cells appeared stellate with numerous slender cytoplasmic processes and degranulated, which is the most obvious after 20 min. In addition, immunopositivity of endothelial and anterior pituitary cells for VP suggests its influence on ACTH secretion.


Incisor crossbite and repaired unilateral cleft lip and palate: changes in jaw movement and temporalis muscle activity before and after edgewise treatment--case report.
To examine the changes in jaw movement and temporalis muscle activity of a patient with unilateral cleft lip and palate before and after edgewise treatment. Clinical case study. University dental hospital, department of orthodontics. A 12-year 3-month-old male with incisor crossbite, molar malocclusion, and repaired unilateral cleft lip and palate who had completed first-phase orthodontic treatment. This patient was treated with an edgewise appliance. Jaw movement and temporalis muscle activity during the chewing of a hard gummy jelly were recorded at 2 kHz from the sixth to the twentieth stroke before edgewise treatment and after a retention period of 2 years. Optimum intercuspation of teeth was achieved. The reversed crossing jaw-movement pattern before treatment changed to a normal grinding after treatment. The posterior temporalis muscle on the chewing side exhibited an earlier burst than the contralateral one during chewing at the post-treatment stage, as is observed in cases with good occlusion. Improvement in the occlusion using an edgewise appliance is necessary for acquiring a good masticatory function in patients with incisor crossbite, molar malocclusion, and cleft lip and palate.


Benzylic Radical Stabilization Permits Ether Formation During Darobactin Biosynthesis.
The Gram-negative selective antibiotic darobactin A has attracted interest owing to its intriguing fused bicyclic structure and unique mode of action. Biosynthetic studies have revealed that darobactin is a ribosomally synthesized and post-translationally modified peptide (RiPP). During maturation, the darobactin precursor peptide (DarA) is modified by a radical S -adenosyl methionine (rSAM)-dependent enzyme (DarE) to contain ether and C-C crosslinks. In this work, we describe the enzymatic tolerance of DarE using a panel of DarA variants, revealing that DarE can install the ether and C-C crosslinks independently and in different locations on DarA. These efforts produced 57 darobactin variants, 50 of which were enzymatically modified. Several new variants with fused bicyclic structures were characterized, including darobactin W3Y, which replaces tryptophan with tyrosine at the twice-modified central position, and darobactin K5F, which displays a fused diether ring pattern. Three additional darobactin variants contained fused diether macrocycles, leading us to investigate the origin of ether versus C-C crosslink formation. Computational analyses found that more stable and long-lived Cβ radicals found on aromatic amino acids correlated with ether formation. Further, molecular docking and calculated transition state structures provide support for the different indole connectivity observed for ether (Trp-C7) and C-C (Trp-C6) crosslink formation. We also provide experimental evidence for a β-oxotryptophan modification, a proposed intermediate during ether crosslink formation. Finally, mutational analysis of the DarA leader region and protein structural predictions identified which residues were dispensable for processing and others that govern substrate engagement by DarE. Our work informs on darobactin scaffold engineering and sheds additional light on the underlying principles of rSAM catalysis.


Recombinant cell ultrasensitive bioassay for measurement of estrogens in postmenopausal women.
A recent analysis of data from nine studies provided convincing evidence that plasma estradiol measurements predict the risk of breast cancer in normal postmenopausal women. However, the median values detected by the various assays used in this study varied by 5-fold. These and other published data in normal postmenopausal women suggest that assays measuring low plasma estradiol concentrations suffer from problems of sensitivity, specificity, and precision. Availability of a practical, low-cost, specific, precise, and ultrasensitive estrogen assay might allow enhanced prediction of the risk of breast cancer and provide an objective means of selecting postmenopausal women for breast cancer prevention. A recombinant cell ultrasensitive bioassay (RCUB) for estrogen was recently validated for use in prepubertal children. We postulated that the RCUB might also prove useful for measurement of postmenopausal levels and designed the present study to examine this possibility. Thirty normal postmenopausal volunteers provided blood samples for measurement of estrogen by RCUB and, for comparison, by RIA. The estrogenic activity measured by RCUB [mean +/- sd, 11.9 +/- 10.9 pmol/liter (SI units, 3.23 +/- 2.96 pg/ml] was significantly lower than estradiol levels measured by RIA [43.7 +/- 44.0 pmol/liter (11.9 +/- 12.0 pg/ml)] in our volunteer subjects (P < 0.00001). Nonetheless, plasma estradiol levels measured by bioassay were significantly correlated with the estrogenic activity measured by RIA (r = 0.84) and by gas chromatography/tandem mass spectrometry (r = 0.85). To obtain biological evidence of the validity of the RCUB, we related plasma estrogen levels to body weight and body mass index and found highly significant correlations (r = 0.54 and r = 0.53, respectively). Surprisingly, 28 of 30 postmenopausal women were found to have estrogen levels in the prepubertal range with the RCUB. The levels detected by RCUB were similar to those previously reported using an ultrasensitive but less practical yeast bioassay. These results provide validation for the RCUB in postmenopausal women and suggest that it might prove useful for selection of women for drug therapy to prevent breast cancer.


Cross-talk reduction in a multiplexed synchroscan streak camera with simultaneous calibration.
The streak camera is a picosecond resolution photodetector with parallel input capability; however, the degree of multiplexing is limited by crosstalk and temporal uncertainty in the sweeping field. We introduced a fixed time delay between adjacent fibers to reduce crosstalk in the synchroscan mode. The fixed delay and a tunable electronic delay between the input pulse and the synchroscan unit allows robust separation modes between the streaks, while spatial and temporal nonlinearities can be calibrated in. The efficacy of the design is demonstrated through a 100-fold multiplexed confocal fluorescence lifetime imaging microscope in live cells.


Retinal Anatomy and Electrode Array Position in Retinitis Pigmentosa Patients After Argus II Implantation: An International Study.
To assess the retinal anatomy and array position in Argus II retinal prosthesis recipients. Prospective, noncomparative cohort study. Setting: International multicenter study. Argus II recipients enrolled in the Post-Market Surveillance Studies. Spectral-domain optical coherence tomography images collected for the Surveillance Studies (NCT01860092 and NCT01490827) were reviewed. Baseline and postoperative macular thickness, electrode-retina distance (gap), optic disc-array overlap, and preretinal membrane presence were recorded at 1, 3, 6, and 12 months. Axial retinal thickness and axial gap along the array's long axis (a line between the tack and handle); maximal retinal thickness and maximal gap along a B-scan near the tack, midline, and handle. Thirty-three patients from 16 surgical sites in the United States and Germany were included. Mean axial retinal thickness increased from month 1 through month 12 at each location, but reached statistical significance only at the array midline (P = .007). The rate of maximal thickness increase was highest near the array midline (slope = 6.02, P = .004), compared to the tack (slope = 3.60, P < .001) or the handle (slope = 1.93, P = .368). The mean axial and maximal gaps decreased over the study period, and the mean maximal gap size decrease was significant at midline (P = .032). Optic disc-array overlap was seen in the minority of patients. Preretinal membranes were common before and after implantation. Progressive macular thickening under the array was common and corresponded to decreased electrode-retina gap over time. By month 12, the array was completely apposed to the macula in approximately half of the eyes.


The value of the PinPoint ion chamber for characterization of small field segments used in intensity-modulated radiotherapy.
Volume averaging and lack of electronic equilibrium complicate accurate dosimetry of small photon fields. In this paper the performance of the PinPoint ion chamber for characterizing small fields used in intensity-modulated radiotherapy (IMRT) was investigated and the results were compared with those obtained using the Markus ion chamber and a diamond detector. Sharp beam penumbras were measured for a 5 x 5 cm field defined using a cerrobend block mounted on the accelerator head. In addition, output factors were measured for a 6 MV photon beam and a variety of small rectangular fields collimated widthwise using the multileaf collimator (MLC) in combination with the back-up jaws. From this study, a reference field of 5 x 5 cm and a measuring depth of 5 cm are recommended. This is related to the over-response of the PinPoint chamber to low-energy Compton scattered photons, an effect that was investigated rigorously and turned out to limit the scope of this ionization chamber. However, taking into account some limitations, the PinPoint chamber is an excellent detector for output measurements in small fields down to 2 cm. In profile measurements the chamber causes a broadening of the measured penumbras but its spatial resolution is superior to that of the Markus chamber.


[Altered water fractions in the blood and its components after drowning].
Previous studies have shown that signs of drowning in fresh water are of low diagnostic value. Regardless of the mechanism of drowning death, a certain amount of water enters the blood and somehow changes its composition. The objective of this study was to determine water fractions in the blood of drowned subjects. It included 30 cases of drowning deaths. The control group comprised 30 cases of hanging and 7 bodies found in water after the death on land. The water content in the blood was measured in accordance with the universally accepted diagnostic procedure from the difference of freezing temperatures of free and bound water. It was shown that arterial blood and its constituent components as well as whole venous blood and concentrated red cells mass of drowned subjects contained significantly more water than the blood of those who died on land. The rise was in the first place attributable to the selective increase of the free water fraction. Changes of water content in the blood were virtually identical in the drowned subjects who died from asphyxia and from aspiration of water. The data obtained in this study may be used as additional diagnostic signs of drowning death.


A multisensory posture control model of human upright stance.
We present a multisensory postural control model based on experiments where the balance in normal subjects and vestibular loss patients was perturbed by application of external torque produced by force-controlled pull stimuli. The stimuli were applied while subjects stood on a stationary or body-sway-referenced motion platform with eyes closed and auditory cues masked. Excursions of the center of mass (COM) and the center of pressure (COP) were analyzed using a systems analysis approach. The results were compared to an 'inverted pendulum' model of posture control. The model receives input from four sensors: ankle proprioceptors, semicircular canals, otoliths, and plantar pressure sensors (somatosensory graviceptors). Sensor fusion mechanisms are used to yield separate internal representations of foot support motion, gravity, and external torque (pull). These representations are fed as global set point signals into a local control loop based on ankle proprioceptive negative feedback. This set point control upgrades the proprioceptive body-on-foot (support) stabilization into a body-in-space control which compensates for support tilt, gravity, and contact forces. This compensation occurs even when the stimuli are combined or a voluntary lean is superimposed. Model simulations paralleled our experimental findings.


Automated Categorization of Multiclass Welding Defects Using the X-ray Image Augmentation and Convolutional Neural Network.
The detection of weld defects by using X-rays is an important task in the industry. It requires trained specialists with the expertise to conduct a timely inspection, which is costly and cumbersome. Moreover, the process can be erroneous due to fatigue and lack of concentration. In this context, this study proposes an automated approach to identify multi-class welding defects by processing the X-ray images. It is realized by an intelligent hybridization of the data augmentation techniques and convolutional neural network (CNN). The proposed data augmentation mainly performs random rotation, shearing, zooming, brightness adjustment, and horizontal flips on the intended images. This augmentation is beneficial for the realization of a generalized trained CNN model, which can process the multi-class dataset for the identification of welding defects. The effectiveness of the proposed method is confirmed by testing its performance in processing an industrial dataset. The intended dataset contains 4479 X-ray images and belongs to six groups: cavity, cracks, inclusion slag, lack of fusion, shape defects, and normal defects. The devised technique achieved an average accuracy of 92%. This indicates that the approach is promising and can be used in contemporary solutions for the automated detection and categorization of welding defects.


Urbanization and international trade and investment policies as determinants of noncommunicable diseases in Sub-Saharan Africa.
There are three dominant globalization pathways affecting noncommunicable diseases in Sub-Saharan Africa (SSA): urbanization, trade liberalization, and investment liberalization. Urbanization carries potential health benefits due to improved access to an increased variety of food imports, although for the growing number of urban poor, this has often meant increased reliance on cheap, highly processed food commodities. Reduced barriers to trade have eased the importation of such commodities, while investment liberalization has increased corporate consolidation over global and domestic food chains. Higher profit margins on processed foods have promoted the creation of 'obesogenic' environments, which through progressively integrated global food systems have been increasingly 'exported' to developing nations. This article explores globalization processes, the food environment, and dietary health outcomes in SSA through the use of trend analyses and structural equation modelling. The findings are considered in the context of global barriers and facilitators for healthy public policy.


Do ternary liquid mixtures exhibit negative main Fick diffusion coefficients?
Experimental data on Fick diffusion coefficients of ternary and higher mixtures depend on the reference frame; those which are in common use are associated with the average velocity either with respect to volume, mass or mole number. In this study, the dependence of diffusion coefficients on the reference frame is thoroughly analyzed for three ternary mixtures of different types. The first one, tetralin-isobutylbenzene-dodecane, can almost be considered as ideal, the second one, cyclohexane-toluene-methanol, exhibits liquid-liquid phase separation and the third one, water-ethanol-triethylene glycol, contains three associating species and is also strongly non-ideal. Experimental diffusion coefficient data sampled in the volume reference frame are transformed to the molar and mass reference frames. The required partial molar volumes are derived from present density measurements. Four additional mixtures are considered along a single or two composition paths. A highlight of this study is the existence of a strong similarity of the main diffusion coefficients in the volume and mass reference frames for all considered mixtures. When the excess volume is small, the coefficients in the molar reference frame are also similar. However, for the mixture with a large excess volume (containing water), the diffusion coefficients in the molar reference frame differ significantly, even indicating negative main diffusion coefficients. It is shown that negative main diffusion coefficients appear due to relatively large experimental uncertainties of cross diffusion coefficients, which are propagated and amplified by frame transformation.


The use of by-products from metallurgical and mineral industries as filler in cement-based materials.
This investigation has been made in order to make it possible to increase the use of by-products in cement-based materials. Use of by-products requires a screening procedure that will reliably determine their impact on concrete. A test procedure was developed. The most important properties were considered to be strength development, shrinkage, expansion and workability. The methods used were calorimetry, flow table tests, F-shape measurements, measurements of compressive and flexural strength and shrinkage/expansion measurements. Scanning electron microscopy was used to verify some results. Twelve by-products were collected from Swedish metallurgical and mineral industries and classified according to the test procedure. The investigation showed that the test procedure clearly screened out the materials that can be used in the production of concrete from the unsuitable ones.


Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase.
Tec, Btk, Itk, Bmx, and Txk constitute the Tec family of protein tyrosine kinases (PTKs), a family with the distinct feature of containing a pleckstrin homology (PH) domain. Tec acts in signaling pathways triggered by the B cell antigen receptor (BCR), cytokine receptors, integrins, and receptor-type PTKs. Although upstream regulators of Tec family kinases are relatively well characterized, little is known of the downstream effectors of these enzymes. The yeast two-hybrid system has identified several proteins that interact with the kinase domain of Tec, one of which is now revealed to be a previously unknown docking protein termed BRDG1 (BCR downstream signaling 1). BRDG1 contains a proline-rich motif, a PH domain, and multiple tyrosine residues that are potential target sites for Src homology 2 domains. In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Efficient phosphorylation of BRDG1 by Tec required the PH and SH2 domains as well as the kinase domain of the latter. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 transcripts are abundant in the human B cell line Ramos, and the endogenous protein underwent tyrosine phosphorylation in response to BCR stimulation. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.


Chemical synthesis and molecular pharmacology of hydroxylated 1-(1-phenylcyclohexyl-piperidine derivatives.
The following monohydroxy derivatives of 1-(1-phenylcyclohexyl)piperidine (phencyclidine, PCP) were synthesized: o-, m-, and p-phenols of PCP, 1-(1-phenylcyclohexyl)-4-piperidinol, and two stereoisomeric pairs of 3-phenyl-3-(1-piperidinyl)cyclohexanol and 4-phenyl-4-(1-piperidinyl)cyclohexanol. Inhibition of specific binding of tritiated PCP, morphine, or quinuclidinyl benzylate (QNB) in rat brain homogenates was measured for these compounds. Inhibition of PCP binding for selected compounds correlated with mouse rotarod assay activity. The most characteristic effects of hydroxylation of PCP on the cyclohexyl, piperidine, or phenyl moieties are the following: (i) it generally decreases its activity in inhibiting [3H]PCP binding by a factor of 10 to 80; (ii) it does not produce a large variation in the affinity for the morphine receptor; (iii) it produces a considerable decrease of the affinity for the muscarinic receptor. An important exception to these general observations was the metaphenolic derivative of PCP. This PCP derivative has an affinity for the [3H]PCP binding sites that is 8 times higher than that of PCP itself; its affinity for the muscarinic receptor is only twice lower than that of PCP, but its affinity for the morphine receptor is 430 times higher than that of PCP and only one order of magnitude lower than that of morphine itself.


Multi-finger synergies and the muscular apparatus of the hand.
We explored whether the synergic control of the hand during multi-finger force production tasks depends on the hand muscles involved. Healthy subjects performed accurate force production tasks and targeted force pulses while pressing against loops positioned at the level of fingertips, middle phalanges, and proximal phalanges. This varied the involvement of the extrinsic and intrinsic finger flexors. The framework of the uncontrolled manifold (UCM) hypothesis was used to analyze the structure of inter-trial variance, motor equivalence, and anticipatory synergy adjustments prior to the force pulse in the spaces of finger forces and finger modes (hypothetical finger-specific control signals). Subjects showed larger maximal force magnitudes at the proximal site of force production. There were synergies stabilizing total force during steady-state phases across all three sites of force production; no differences were seen across the sites in indices of structure of variance, motor equivalence, or anticipatory synergy adjustments. Indices of variance, which did not affect the task (within the UCM), correlated with motor equivalent motion between the steady states prior to and after the force pulse; in contrast, variance affecting task performance did not correlate with non-motor equivalent motion. The observations are discussed within the framework of hierarchical control with referent coordinates for salient effectors at each level. The findings suggest that multi-finger synergies are defined at the level of abundant transformation between the low-dimensional hand level and higher dimensional finger level while being relatively immune to transformations between the finger level and muscle level. The results also support the scheme of control with two classes of neural variables that define referent coordinates and gains in back-coupling loops between hierarchical control levels.


Curcumin, Gut Microbiota, and Neuroprotection.
Curcumin, a nontoxic, naturally occurring polyphenol, has been recently proposed for the management of neurodegenerative and neurological diseases. However, a discrepancy exists between the well-documented pharmacological activities that curcumin seems to possess in vivo and its poor aqueous solubility, bioavailability, and pharmacokinetic profiles that should limit any therapeutic effect. Thus, it is possible that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of curcumin are present after oral administration. Indeed, a new working hypothesis that could explain the neuroprotective role of curcumin despite its limited availability is that curcumin acts indirectly on the central nervous system by influencing the "microbiota-gut-brain axis", a complex bidirectional system in which the microbiome and its composition represent a factor which preserves and determines brain "health". Interestingly, curcumin and its metabolites might provide benefit by restoring dysbiosis of gut microbiome. Conversely, curcumin is subject to bacterial enzymatic modifications, forming pharmacologically more active metabolites than curcumin. These mutual interactions allow to keep proper individual physiologic functions and play a key role in neuroprotection.


Chromosome phylogeny of the subfamily Pitheciinae (Platyrrhini, Primates) by classic cytogenetics and chromosome painting.
The New World monkey (Platyrrhini) subfamily Pitheciinae is represented by the genera Pithecia, Chiropotes and Cacajao. In this work we studied the karyotypes of Pithecia irrorata (2n = 48) and Cacajao calvus rubicundus (2n = 45 in males and 2n = 46 in females) by G- and C-banding, NOR staining and chromosome painting using human and Saguinus oedipus whole chromosome probes. The karyotypes of both species were compared with each other and with Chiropotes utahicki (2n = 54) from the literature. Our results show that members of the Pitheciinae have conserved several chromosome forms found in the inferred ancestral Platyrrhini karyotype (associations of human homologous segments 3a/21, 5/7a, 2b/16b, 8a/18, 14/15a and 10a/16a). Further, the monophyly of this subfamily is supported by three chromosomal synapomorphies (2a/10b, an acrocentric 15/14 and an acrocentric human 19 homolog). In addition, each species presents several autapomorphies. From this data set we established a chromosomal phylogeny of Pitheciinae, resulting in a single most parsimonious tree. In our chromosomal phylogeny, the genus Pithecia occurred in a more basal position close to the inferred ancestor of Platyrrhini, while C. c. rubicundus and C. utahicki are closely related and are linked by exclusive synapomorphies.


HSP110 translocates to the nucleus upon genotoxic chemotherapy and promotes DNA repair in colorectal cancer cells.
A multicenter clinical study demonstrated the presence of a loss-of-function HSP110 mutation in about 15% of colorectal cancers, which resulted from an alternative splicing and was produced at the detriment of wild-type HSP110. Patients expressing low levels of wild-type HSP110 had excellent outcomes (i.e. response to an oxaliplatin-based chemotherapy). Here, we show in vitro, in vivo, and in patients' biopsies that HSP110 co-localizes with DNA damage (γ-H2AX). In colorectal cancer cells, HSP110 translocates into the nucleus upon treatment with genotoxic chemotherapy such as oxaliplatin. Furthermore, we show that HSP110 interacts with the Ku70/Ku80 heterodimer, an essential element of the non-homologous end joining (NHEJ) repair machinery. We also demonstrate by evaluating the resolved 53BP1 foci that depletion in HSP110 impairs repair steps of the NHEJ pathway, which is associated with an increase in DNA double-strand breaks and in the cells' sensitivity to oxaliplatin. HSP110-depleted cells sensitization to oxaliplatin-induced DNA damage is abolished upon re-expression of HSP110. Confirming a role for HSP110 in DNA non-homologous repair, SCR7 and NU7026, two inhibitors of the NHEJ pathway, circumvents HSP110-induced resistance to chemotherapy. In conclusion, HSP110 through its interaction with the Ku70/80 heterodimer may participate in DNA repair, thereby inducing a protection against genotoxic therapy.


Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice.
Enteric neurons express oxytocin (OT); moreover, enteric neurons and enterocytes express developmentally regulated OT receptors (OTRs). Although OT (with secretin) opposes intestinal inflammation, physiological roles played by enteric OT/OTR signaling have not previously been determined. We tested hypotheses that OT/OTR signaling contributes to enteric nervous system (ENS)-related gastrointestinal (GI) physiology. GI functions and OT effects were compared in OTR-knockout (OTRKO) and wild-type (WT) mice. Stool mass and water content were greater in OTRKO mice than in WT. GI transit time in OTRKO animals was faster than in WT; OT inhibited in vitro generation of ENS-dependent colonic migrating motor complexes in WT but not in OTRKO mice. Myenteric neurons were hyperplastic in OTRKO animals, and mucosal exposure to cholera toxin (CTX) in vitro activated Fos in more myenteric neurons in OTRKO than WT than in WT mice; OT inhibited the CTX response in WT but not in OTRKO mice. Villi and crypts were shorter in OTRKO than in WT mice, and transit-amplifying cell proliferation in OTRKO crypts was deficient. Macromolecular intestinal permeability in OTRKO was greater than WT mice, and experimental colitis was more severe in OTRKO mice; moreover, OT protected WT animals from colitis. Observations suggest that OT/OTR signaling acts as a brake on intestinal motility, decreases mucosal activation of enteric neurons, and promotes enteric neuronal development and/or survival. It also regulates proliferation of crypt cells and mucosal permeability; moreover OT/OTR signaling is protective against inflammation. Oxytocinergic signaling thus appears to play an important role in multiple GI functions that are subject to neuronal regulation.


Photochemical organocatalytic enantioselective radical γ-functionalization of α-branched enals.
Reported herein is a rare example of asymmetric catalytic functionalisation of enals at the remote γ-position, proceeding via a radical path. The process requires visible light and exploits the synergistic actions of two distinct organocatalysts. A nucleophilic organic catalyst generates radicals upon SN2-based activation of commercially available alkyl halides and blue light irradiation. Concomitantly, a chiral secondary amine catalyst triggers the formation of a dienamine from α-branched enals. This chiral dienamine intercepts the photogenerated radicals with excellent γ-selectivity and good stereocontrol.


Motor Control Changes after Utilizing Upper Extremity Myoelectric Powered Wearable Orthotics in Persons with Acute SCI.
Following spinal cord injury (SCI), upper extremity (UE) weakness may impede one's ability to carry out activities of daily living (ADLs). Such a limitation drastically lowers a person's level of independence. Additionally, therapy and the field of assistive technology continue to place a strong premium on the restoration of UE motor function in patients with SCI. The main objective of this study was to assess the benefits of an UE myoelectric-powered wearable orthosis (MPWO) produced by MyoMo, Inc. (Boston, MA) on improving UE motor function in order to enhance ADLs and quality of life in individuals with subacute SCI. A 43-year-old man with subacute incomplete SCI (iSCI), American Spinal Injury Association (ASIA) Impairment Scale (AIS) C grade received 18 sessions (over a period of six weeks) of UE mobility therapy utilizing the MPWO. The MPWO was used to enhance active range of motion (AROM) of the hand and elbow, and associated muscle activations. After training with the MPWO, hand and elbow AROM and muscle activations were enhanced. These preliminary findings imply that UE-MPWO device-assisted rehabilitation may increase participants' UE activities, leading to improved function.Clinical Relevance- These preliminary findings from a person with iSCI in the subacute phase indicate that training with UE-MPWO assistive devices may enhance UE use during ADLs for people with muscle weakness but still having some residual voluntary muscle activation ability.


The role of genetic polymorphisms in metabolism of carcinogenic heterocyclic aromatic amines.
More than twenty heterocyclic aromatic amines (HAAs) have been identified in grilled meats, fish, poultry, and tobacco smoke condensate. HAAs are carcinogens and induce tumors at multiple sites in experimental laboratory animals. Because of the widespread occurrence of HAAs in foods, these chemicals may contribute to the etiology of several common human cancers that are associated with frequent consumption of grilled meats including colon, rectum, prostate, and breast. HAAs require metabolism in order to exert their genotoxic effects. Metabolic activation occurs by N-hydroxylation, a reaction catalyzed by cytochromes p450 (CYP). Some N-hydroxy-HAA metabolites may directly react with DNA, but further metabolism by N-acetyltransferases (NATs) or sulfotransferases (SULTs) may occur to form highly reactive N-acetoxy or N-sulfonyloxy esters that readily react with DNA bases. The N-acetoxy ester of the HAA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is detoxified by glutathione S-transferases (GSTs), which catalyze the reduction of the reactive intermediate back to the parent amine. Some HAAs also undergo detoxification through conjugation reactions with the phase II enzymes such as UDP-glucuronosyltransferases (UGTs) or SULTs to form stable, polar products that are readily eliminated. All of these xenobiotic metabolism enzyme systems (XMEs) display common genetic polymorphisms, which may affect protein expression, protein stability, catalytic activity, and thus, the biological potency of these procarcinogens. In this review, the roles of common genetic polymorphisms of XMEs involved in HAA metabolism and cancer risk are discussed.


Myasthenia gravis induced or exacerbated by immune checkpoint inhibitors: a rising concern.
Immune checkpoint inhibitors can cause immune side effects, with myasthenia gravis (MG) being relatively rare. With this review, we present 66-year-old man with melanoma treated with pembrolizumab who developed MG. With immuno-oncology (IO) single agent usage, 42 cases reported new-onset MG and 9 cases reported exacerbation of pre-existing MG. Among the patients who had new-onset MG after administration of programmed cell death protein 1 (PD-1) inhibitors, 14 patients (38.8%) developed severe respiratory failure and required intubation and 10 patients (27.02%) died. Among the patients with exacerbation of pre-existing MG after receiving PD-1 inhibitors, 1 patient (11.1%) required intubation, and no death was reported. Combination IO therapy-induced MG was reported in seven cases, with at least two cases complicated by respiratory failure and one death. Our observations suggest a possible difference in the severity of the disease and outcome among different IO therapy options.


Adrenomedullin expression by gastric epithelial cells in response to infection.
Many surface epithelial cells express adrenomedullin, a multifunctional peptide found in a wide number of body and cell systems. Recently, we and others have proposed that adrenomedullin has an important novel role in host defense. This peptide has many properties in common with other cationic antimicrobial peptides, including the human beta-defensins. Upon exposure of human gastric epithelial cells to viable cells of invasive or noninvasive strains of Helicobacter pylori, Escherichia coli, Salmonella enterica, or Streptococcus bovis, a significant increase in adrenomedullin secretion from these cells was demonstrated. Adrenomedullin gene expression was also increased in response to these microorganisms. Similar observations were noted when these cells were incubated with proinflammatory cytokines such as interleukin 1 alpha (IL-1 alpha), IL-6, tumor necrosis factor alpha and lipopolysaccharide. In cultured cells and an animal infection model, increased adrenomedullin peptide and gene expression was demonstrated when exposed to E. coli or Mycobacterium paratuberculosis, respectively. The data suggest there is a strong association between epithelial infection, inflammation, and adrenomedullin expression, which may have clinical relevance. The regulation of adrenomedullin expression may have therapeutic applications, such as improving or enhancing mucosal immunity.


Characteristics of cultured human melanocytes isolated from different stages of tumor progression.
Normal melanocytes and melanocytes of normal nevi, primary melanoma in the radial (RGP) and vertical (VGP) growth phases, and metastatic melanoma exhibited and maintained phenotypic differences when grown in tissue culture or in experimental animals. Only metastatic and VGP primary melanoma cells were tumorigenic in athymic nude mice and had nonrandom chromosomal abnormalities involving chromosomes 1, 6, and 7. The colony-forming efficiency in soft agar was also highest in these two cell types. A cell line of RGP primary melanoma had characteristics of both benign and malignant cells: nevus-like morphology; nontumorigenicity in nude mice; but karyotypic abnormality of chromosome 6. It also had a ganglioside pattern similar to that of normal melanocytes but not melanomas, i.e., a high GM3 ganglioside content compared to the amounts of GM2, GD2, and GD3 gangliosides. Binding of monoclonal antibodies secreted by hybridomas generated by immunization of mice with VGP primary and metastatic melanoma was highest with cells and supernatants of cultures from advanced melanoma and least with nevus cells. There was no binding to normal melanocytes except with the monoclonal antibodies specific for nerve growth factor receptor or 9-O-acetyl-GD3 ganglioside. On the other hand, monoclonal anti-nevus antibodies bound to melanocytes, nevus cells, and RGP primary melanoma cells but not to VGP primary or metastatic melanoma cells. Cultured human melanocytic cells appear to be a unique model for the study of tumor progression.


The pattern of fatty acid synthesis in lactating rabbit mammary gland studied in vivo.
The biosynthesis of fatty acids has been studied in lactating rabbits at 6h after intravenous injection of sodium [1-(14)C]acetate. The specific radioactivities of the individual fatty acids (C(6:0) to C(14:0)) and the proportions of these fatty acids synthesized were similar in mammary tissue and milk. Hexanoic acid had the highest specific radioactivity, and the C(8:0)-C(14:0) fatty acids had similar specific radioactivities, which were about five times those of C(16) and C(18) acids. No radioactivity was detected in fatty acids of chain length <C(14) in the liver, blood or adipose tissue and the specific radioactivities of fatty acids of chain length >C(14) in these tissues were similar to those of the long-chain fatty acids in the milk and mammary gland. The results show that the C(4:0)-C(14:0) fatty acids are synthesized within the mammary gland rather than by fatty acid uptake from circulating blood or by oxidation of long-chain fatty acids within the gland. We conclude that de novo synthesis of esterified fatty acids in vivo by this tissue has a high degree of chain-length specificity.


Community-associated methicillin-resistant Staphylococcus aureus in Indigenous communities in Canada.
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have emerged as a significant issue in some Indigenous communities (including First Nations, Inuit and Métis) in Canada. Primarily associated with skin and soft-tissue infections, this organism can also result in significant morbidity and mortality. Canadian and American guidelines for managing CA-MRSA infections have been published. The specific epidemiology, microbiology and susceptibility patterns, and the social/environmental circumstances of CA-MRSA infections in Indigenous communities need to be considered for strategies to reduce transmission. While reducing household crowding and improving in-home potable water supply are optimal strategies to reduce the impact of this illness, implementing Canadian guidelines along with increased prevention strategies are recommended as interim measures.


A machine learning model for the prediction of survival and tumor subtype in pancreatic ductal adenocarcinoma from preoperative diffusion-weighted imaging.
To develop a supervised machine learning (ML) algorithm predicting above- versus below-median overall survival (OS) from diffusion-weighted imaging-derived radiomic features in patients with pancreatic ductal adenocarcinoma (PDAC). One hundred two patients with histopathologically proven PDAC were retrospectively assessed as training cohort, and 30 prospectively accrued and retrospectively enrolled patients served as independent validation cohort (IVC). Tumors were segmented on preoperative apparent diffusion coefficient (ADC) maps, and radiomic features were extracted. A random forest ML algorithm was fit to the training cohort and tested in the IVC. Histopathological subtype of tumor samples was assessed by immunohistochemistry in 21 IVC patients. Individual radiomic feature importance was evaluated by assessment of tree node Gini impurity decrease and recursive feature elimination. Fisher's exact test, 95% confidence intervals (CI), and receiver operating characteristic area under the curve (ROC-AUC) were used. The ML algorithm achieved 87% sensitivity (95% IC 67.3-92.7), 80% specificity (95% CI 74.0-86.7), and ROC-AUC 90% for the prediction of above- versus below-median OS in the IVC. Heterogeneity-related features were highly ranked by the model. Of the 21 patients with determined histopathological subtype, 8/9 patients predicted to experience below-median OS exhibited the quasi-mesenchymal subtype, whilst 11/12 patients predicted to experience above-median OS exhibited a non-quasi-mesenchymal subtype (p < 0.001). ML application to ADC radiomics allowed OS prediction with a high diagnostic accuracy in an IVC. The high overlap of clinically relevant histopathological subtypes with model predictions underlines the potential of quantitative imaging in PDAC pre-operative subtyping and prognosis.


Enhanced osteoblast differentiation and osseointegration of a bio-inspired HA nanorod patterned pore-sealed MgO bilayer coating on magnesium.
Endosseous magnesium (Mg) and its alloy implants are meeting obstacles due to their fast degradation and the resultant poor cytocompatibility and osseointegration. Herein, a bio-inspired coating (named HT24h), comprising an outer layer of narrow interrod spaced hydroxyapatite (HA) nanorods mimicking the osteoclast-created nanotopography of the bone matrix at remodeling sites and an inner layer of pore-sealed MgO was fabricated on Mg using microarc oxidation (MAO) and hydrothermal treatment (HT). Its effects on in vitro hFOB1.19 cell functions such as proliferation, differentiation and extracellular matrix mineralization as well as in vivo osteogenesis, bone-implant contact, push-out force and pushed-out failure mode assessed osseointegration were investigated, together with porous MgO (MAO0)- and MgO containing Mg(OH)2-sealing-pores (HT2h)-coated Mg. Compared to MAO0- and HT2h-coated Mg, HT24h-coated Mg greatly enhanced osteoblast functions, which is ascribed to the HA nanorod derived up-regulated intracellular Ca2+ and down-regulated intracellular Mg2+ concentrations as well as the lightened H2 evolution and alkalization of the surrounding medium. Owing to the enhanced osteoblast functions, HT24h-coated Mg greatly enhanced osseointegration and its pushed-out failure occurred predominantly within the peri-implant bone rather than within the coating for HT2h-coated Mg and at the coating/Mg interface for MAO0-coated Mg, giving rise to an advanced Mg-based implant with improved clinical performance.


Effect of inclusion of salmon roe on characteristics of salmon baby food products.
Baby food was formulated from sockeye salmon (puree alone, puree + chunks, puree + pink row, puree + pink row + chunks, puree + red row, puree + red roe + chunks). In the 1st study, physical (pH, instrumental color, water activity) and descriptive sensory (odor, flavor, texture, visual color) characteristics were determined. Samples containing roe were lighter and less red (by approximately 3 to 4 a* units) than formulations without roe regardless of the type of roe added. Visual pink color followed the same trend. Formulations with roe, both pink and sockeye, were almost twice as fibrous as formulations without roe. Salmon flavor was stronger in samples containing roe from sockeye salmon. In the 2nd study, retort processed samples were stored at room temperature for 6 mo. Sweaty odor decreased over storage time. Visual cream-brown color correlated with L*, a*, b*, and chroma values (r =-0.80, 0.75, 0.80, and 0.84, respectively). TBARS values of all samples were < 0.35 mg MDA/kg and declined after month 0 indicating that these products were oxidatively stable. Overall, adding roe to these products lightened them and increased fibrous texture. Samples containing sockeye salmon roe had stronger salmon flavor. Once retort processed, these products were quite stable in terms of color, odor, and TBARS. Potential nutrient contributions of this type of product to the infant diet warrant additional research.


Population genetics and historical demographic inferences of the blue crab Callinectes sapidus in the US based on microsatellites.
The native range of the blue crab Callinectes sapidus spans Nova Scotia to northern Argentina. In the US, it constitutes a keystone species in estuarine habitats of the Atlantic coast and Gulf of Mexico (GOM), serving as both predator and prey to other species, and also has historically represented a multi-billion dollar fishery. Knowledge relevant to effective management and monitoring of this ecologically and economically important species, such as levels of population genetic differentiation and genetic diversity, is necessary. Although several population genetics studies have attempted to address these questions in one or more parts of its distribution, conflicting results and potential problems with the markers used, as well as other issues, have obscured our understanding on them. In this study, we examined large-scale genetic connectivity of the blue crab in the US, using 16 microsatellites, and genotyped individuals from Chesapeake Bay, in the US Atlantic, and from nine localities along the US GOM coast. Consistent with the high long-distance dispersal potential of this species, very low levels of genetic differentiation were detected for the blue crab among the ten US localities examined, suggesting it constitutes a large panmictic population within this region. Estimations of genetic diversity for the blue crab appear to be high in the US, and provide a baseline for monitoring temporal changes in this species. Demographic analyses indicate a recent range expansion of the US population, probably during the Holocene. In addition, capitalizing on published microsatellite data from southern Brazil, our analyses detected high genetic differentiation between localities in the US and Brazil. These results point to the need for examination of genetic diversity and differentiation along the area spanning the US to southern Brazil.


Hip Fracture in the Frail Elderly: Making the Case for Early Integration of Palliative Care and Timely Hospice Referral.
With the projected increase of an aging population in the upcoming decades, coupled with increasing elderly longevity, the incidence of hip fractures among this vulnerable population is expected to grow. Current evidence reveals high mortality rates within 6 months to 1 year among frail elderly patients who suffer hip fracture. In addition, the presence of multiple chronic conditions negatively impacts mortality rates in this vulnerable population. The purpose of this article is to discuss both the importance of integrating early palliative care and the appropriateness for hospice referral among frail elderly hip fracture patients. Moreover, the role nurses' play in early recognition of the need for palliative and/or hospice services among this vulnerable population will be explored.


Early identification of patients requiring massive transfusion, embolization, or hemostatic surgery for traumatic hemorrhage: a systematic review protocol.
Hemorrhage is a major cause of early mortality following a traumatic injury. The progression and consequences of significant blood loss occur quickly as death from hemorrhagic shock or exsanguination often occurs within the first few hours. The mainstay of treatment therefore involves early identification of patients at risk for hemorrhagic shock in order to provide blood products and control of the bleeding source if necessary. The intended scope of this review is to identify and assess combinations of predictors informing therapeutic decision-making for clinicians during the initial trauma assessment. The primary objective of this systematic review is to identify and critically assess any existing multivariable models predicting significant traumatic hemorrhage that requires intervention, defined as a composite outcome comprising massive transfusion, surgery for hemostasis, or angiography with embolization for the purpose of external validation or updating in other study populations. If no suitable existing multivariable models are identified, the secondary objective is to identify candidate predictors to inform the development of a new prediction rule. We will search the EMBASE and MEDLINE databases for all randomized controlled trials and prospective and retrospective cohort studies developing or validating predictors of intervention for traumatic hemorrhage in adult patients 16 years of age or older. Eligible predictors must be available to the clinician during the first hour of trauma resuscitation and may be clinical, lab-based, or imaging-based. Outcomes of interest include the need for surgical intervention, angiographic embolization, or massive transfusion within the first 24 h. Data extraction will be performed independently by two reviewers. Items for extraction will be based on the CHARMS checklist. We will evaluate any existing models for relevance, quality, and the potential for external validation and updating in other populations. Relevance will be described in terms of appropriateness of outcomes and predictors. Quality criteria will include variable selection strategies, adequacy of sample size, handling of missing data, validation techniques, and measures of model performance. This systematic review will describe the availability of multivariable prediction models and summarize evidence regarding predictors that can be used to identify the need for intervention in patients with traumatic hemorrhage. PROSPERO CRD42017054589.


Requirements for the implementation of open door policies in acute psychiatry from a mental health professionals' and patients' view: a qualitative interview study.
Treating legally committed patients on open, instead of locked wards is controversially discussed and the affected stakeholders (patients, mental health professionals) have ambiguous views on the benefits and disadvantages. The study aims to assess the opinions and values of relevant stakeholders with regard to the requirements for implementing open wards in psychiatric hospitals. Semi-structured interviews were conducted with 15 psychiatrists, 15 psychiatric nurses and 15 patients, and were analyzed using qualitative content analysis. The interviewees identified conceptual, personnel and spatial requirements necessary for an open door policy. Observation and door watch concepts are judged to be essential for open wards, and patients appreciate the therapeutic value they hold. However, nurses find the door watch problematic. All groups suggest seclusion or small locked divisions as a possible way of handling agitated patients. All stakeholders agree that such concepts can only succeed if sufficient, qualified staff is available. They also agree that freedom of movement is a key element in the management of acutely ill patients, which can be achieved with an open door policy. Finally, the interviewees suggested removing the door from direct view to prevent absconding. For psychiatric institutions seeking to implement (partially) open wards, the present results may have high practical relevance. The stakeholders' suggestions also illustrate that fundamental clinical changes depend on resource investments which - at least at a certain point - might not be feasible for individual psychiatric institutions but presumably require initiatives on the level of mental health care providers or policy makers.


Laboratory screening for erythropoietin abuse in sport: an emerging challenge.
The growing diffusion of banned practice to improve the athletic performances is forcing clinical laboratories to identify and standardize reliable assays to detect potential unfairness. Among the doping practices, the use of recombinant human erythropoietin is becoming fairly popular, due to simplicity and safeties of administration and troublesome detection. The heterogeneous response rate, the presence of a little but significant amount of naturally occurring hormone, the short half-life exhibited by recombinant human erythropoietin and the lack of standardization of commercial assays appear the main problems to overcome. Aim of the present article is to provide a critical review of some of the more widespread laboratory techniques currently available for the screening for erythropoietin abuse in sport.


Sequential E2s drive polyubiquitin chain assembly on APC targets.
The anaphase-promoting complex (APC), or cyclosome, is an E3 ubiquitin-protein ligase that collaborates with E2 ubiquitin-conjugating enzymes to assemble polyubiquitin chains on proteins important for cell-cycle progression. It remains unclear how the APC - or many other E3s - promotes the multiple distinct reactions necessary for chain assembly. We addressed this problem by analyzing APC interactions with different E2s. We screened all budding yeast E2s as APC coenzymes in vitro and found that two, Ubc4 and Ubc1, are the key E2 partners for the APC. These proteins display strikingly different but complementary enzymatic behaviors: Ubc4 supports the rapid monoubiquitination of multiple lysines on APC targets, while Ubc1 catalyzes K48-linked polyubiquitin chain assembly on preattached ubiquitins. Mitotic APC function is lost in yeast strains lacking both Ubc1 and Ubc4. E2-25K, a human homolog of Ubc1, also promotes APC-dependent chain extension on preattached ubiquitins. We propose that sequential E2 proteins catalyze K48-linked polyubiquitination and thus proteasomal destruction of APC targets.


Molecular markers to characterize the hermaphroditic reproductive system of the planarian Schmidtea mediterranea.
The freshwater planarian Schmidtea mediterranea exhibits two distinct reproductive modes. Individuals of the sexual strain are cross-fertilizing hermaphrodites with reproductive organs that develop post-embryonically. By contrast, individuals of the asexual strain reproduce exclusively by transverse fission and fail to develop reproductive organs. These different reproductive strains are associated with distinct karyotypes, making S. mediterranea a useful model for studying germline development and sexual differentiation. To identify genes expressed differentially between these strains, we performed microarray analyses and identified >800 genes that were upregulated in the sexual planarian. From these, we characterized 24 genes by fluorescent in situ hybridization (FISH), revealing their expression in male germ cells or accessory reproductive organs. To identify additional markers of the planarian reproductive system, we also used immuno- and fluorescent lectin staining, identifying several antibodies and lectins that labeled structures associated with reproductive organs. Collectively, these cell-type specific markers will enable future efforts to characterize genes that are important for reproductive development in the planarian.


Ecological Interactions among Thrips, Soybean Plants, and Soybean Vein Necrosis Virus in Pennsylvania, USA.
Analysis of ecological and evolutionary aspects leading to durability of resistance in soybean cultivars against species Soybean vein necrosis orthotospovirus (SVNV) (Bunyavirales: Tospoviridae) is important for the establishment of integrated pest management (IPM) across the United States, which is a leading exporter of soybeans in the world. SVNV is a seed- and thrips- (vector)-borne plant virus known from the USA and Canada to Egypt. We monitored the resistance of soybean cultivars against SVNV, surveyed thrips species on various crops including soybeans in Pennsylvania, and studied thrips overwintering hibernation behavior under field conditions. Field and lab experiments determined disease incidence and vector abundance in soybean genotypes. The impact of the virus, vector, and their combination on soybean physiology was also evaluated. Seed protein, fiber, oil, and carbohydrate content were analyzed using near infra-red spectroscopy. We found that the variety Channel3917R2x had higher numbers of thrips; hence, it was categorized as preferred, while results showed that no variety was immune to SVNV. We found that thrips infestation alone or in combination with SVNV infection negatively impacted soybean growth and physiological processes.


Endometriosis-associated ovarian carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets-a narrative review.
Endometriosis is a benign gynecologic condition affecting up to one woman out of ten of reproductive age. It is defined by the presence of endometrial-like tissue in localizations outside of the uterine cavity. It often causes symptoms such as chronic pain, most frequently associated with the menstrual cycle, and infertility, but may also be oligo- or asymptomatic. There is evidence that some ovarian carcinoma (OC) histotypes, mainly the ovarian clear cell (OCCC) and endometrioid (EnOC) carcinoma, may arise from endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interacting domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which frequently co-occur. In ARID1A deficient cancers preclinical experimental data suggest different targetable mechanisms including epigenetic regulation, cell cycle, genomic instability, the PI3K/AKT/mTOR pathway, inflammatory pathways, immune modulation, or metabolic alterations as potential precision oncology approaches. Most of these strategies are relying on the concept of synthetic lethality in which tumors deficient in ARID1A are more sensitive to the different compounds. Some of these approaches are currently being or have recently been investigated in early clinical trials. The remarkably frequent occurrence of these mutations in endometriosis-associated ovarian cancer, the occurrence in a relatively young population, and the high proportion of platinum-resistant disease certainly warrants further investigation of precision oncology opportunities in this population. Furthermore, advanced knowledge about oncogenic mutations involved in endometriosis-associated ovarian carcinomas may be potentially useful for early cancer detection. However, this approach may be complicated by the frequent occurrence of somatic mutations in benign endometriotic tissue as recent studies suggest. In this narrative review of the current literature, we will discuss the data available on endometriosis-associated ovarian carcinoma, with special emphasis on epidemiology, diagnosis and molecular changes that could have therapeutic implications and clinical applicability in the future.


The effects of modeling simplifications on craniofacial finite element models: the alveoli (tooth sockets) and periodontal ligaments.
Several finite element models of a primate cranium were used to investigate the biomechanical effects of the tooth sockets and the material behavior of the periodontal ligament (PDL) on stress and strain patterns associated with feeding. For examining the effect of tooth sockets, the unloaded sockets were modeled as devoid of teeth and PDL, filled with teeth and PDLs, or simply filled with cortical bone. The third premolar on the left side of the cranium was loaded and the PDL was treated as an isotropic, linear elastic material using published values for Young's modulus and Poisson's ratio. The remaining models, along with one of the socket models, were used to determine the effect of the PDL's material behavior on stress and strain distributions under static premolar biting and dynamic tooth loading conditions. Two models (one static and the other dynamic) treated the PDL as cortical bone. The other two models treated it as a ligament with isotropic, linear elastic material properties. Two models treated the PDL as a ligament with hyperelastic properties, and the other two as a ligament with viscoelastic properties. Both behaviors were defined using published stress-strain data obtained from in vitro experiments on porcine ligament specimens. Von Mises stress and strain contour plots indicate that the effects of the sockets and PDL material behavior are local. Results from this study suggest that modeling the sockets and the PDL in finite element analyses of skulls is project dependent and can be ignored if values of stress and strain within the alveolar region are not required.


Screening tests for pathogenic corynebacteria.
To provide simple tests that would help in the identification of corynebacteria that produce diphtheria toxin. A collection of 99 freshly isolated corynebacteria was assembled and the cultures identified by conventional tests confirmed by an identification kit. Modifications were made to procedures for preparation of the culture medium for the Elek test and to the test for detection of pyrazinamidase (pyrazine carboxylamidase) activity. These two together with an indicator medium for cystinase activity were applied to the collection of organisms. Cystinase was detected in all 61 members of the toxigenic species and none produced pyrazinamidase. In contrast, all but two of the 38 representatives of non-toxigenic species yielded pyrazinamidase and none formed cystinase. Of the 61 cystinase producing cultures (which were also pyrazinamidase negative), 21 gave a positive Elek test with the modified culture medium. A total of 30 of these 61 were tested for toxigenicity in guinea pigs and the results of the animal and plate tests concorded. At least seven cultures could have been reported as non-toxigenic if Elek tests based on media prepared in the conventional way had been the only test available. The three procedures described go some way towards meeting the needs of diagnostic laboratories for efficient procedures for distinguishing pathogenic corynebacteria.


HMA4 expression in tobacco reduces Cd accumulation due to the induction of the apoplastic barrier.
Ectopic expression in tobacco (Nicotiana tabacum v. Xanthi) of the export protein AtHMA4 (responsible in Arabidopsis for the control of Zn/Cd root to shoot translocation) resulted in decreased Cd uptake/accumulation in roots and shoots. This study contributes to understanding the mechanisms underlying this Cd-dependent phenotype to help predict the consequences of transgene expression for potential phytoremediation/biofortification-based strategies. Microarray analysis was performed to identify metal homeostasis genes that were differentially expressed in roots of Cd-exposed AtHMA4-expressing tobacco relative to the wild type. It was established that down-regulation of genes known to mediate Cd uptake was not responsible for reduced Cd uptake/accumulation in AtHMA4 transformants. The transcript levels of NtIRT1 and NtZIP1 were higher in transgenic plants, indicating an induction of the Fe and Zn deficiency status due to AtHMA4 expression. Interestingly, upon exposure to Cd, genes involved in cell wall lignification (NtHCT, NtOMET, and NtPrx11a) were up-regulated in transformants. Microscopic analysis of roots demonstrated that expression of AtHMA4 caused an induction of cell wall lignification in the external cell layers that was accompanied by enhanced H2O2 accumulation. Further study showed that the concentration of other elements (B, Co, Cu, Ni, Mo, and Zn) was reduced in AtHMA4 transformants in the presence of Cd. In conclusion, due to ectopic expression of 35S::AtHMA4, the physical apoplastic barrier within the external cell layer developed, which is likely to be responsible for the reduction of Cd uptake/accumulation.


Cultural Differences in Personality and Aggressive Behavior in Intimate Partner Violence Offenders: A Comparison of English and Spanish Offenders.
Intimate partner violence (IPV) is a ubiquitous and serious problem, the prevalence of which varies greatly around the world. Previous research shows that cultural factors interact with personality and that this interaction influences cognitions, attitudes, and behaviors that are related to personal and individual styles of resolving conflicts. In relation to this, the present study has three aims: comparing the self-reported IPV (physical, psychological and sexual) of English and Spanish offenders, comparing the Millon Clinical Multiaxial Inventory III (MCMI-III) scores of the two groups, and examining the association between country of origin, psychopathology, and IPV. The sample consists of 147 IPV offenders (80 English and 67 Spanish). The measures used were the MCMI-III and the Conflict Tactics Scale 2. The Mann-Whitney U tests were used to compare the English and Spanish sample, and independent logistic regressions were used to examine the relationship between personality patterns, psychopathology and culture, and IPV. Higher frequencies of physical and psychological aggression were found in the English group compared with the Spanish group as well as several differences in personality patterns and psychopathology between the groups. Some MCMI-III subscales also interact with nationality and predict physical and psychological aggression. The relevance of these results for intervention is discussed.


Treatment of wastewater from red and tropical fruit wine production by zeolite anaerobic fluidized bed reactor.
A study of the anaerobic treatment of wastewaters derived from red (RWWW) and tropical fruit wine (TFWWW) production was carried out in four laboratory-scale fluidized bed reactors with natural zeolite as bacterial support. These reactors operated at mesophilic temperature (35 degrees C). Reactors R1 and R2 contained Chilean natural zeolite, while reactors R3 and R4 used Cuban natural zeolite as microorganism support. In addition, reactors R1 and R3 processed RWWW, while reactors R2 and R4 used TFWWW as substrate. The biomass concentration attached to zeolites in the four reactors studied was found to be in the range of 44-46 g volatile solids (VS)/L after 90 days of operation time. Both types of zeolites can be used indistinctly in the fluidized bed reactors achieving more than 80%-86% chemical oxygen demand (COD) removals for organic loading rates (OLR) of up to at least 20 g COD/L d. pH values remained within the optimal range for anaerobic microorganisms for OLR values of up to 20 and 22 g COD/L d for RWWW and TFWWW, respectively. Toxicity and inhibition levels were observed at an OLR of 20 g COD/L d in reactors R1 and R3 while processing RWWW, whereas the aforementioned inhibitory phenomena were not observed at an OLR of 24 g COD/L d in R2 and R4, treating TFWWW as a consequence of the lower phenolic compound content present in this substrate. The volatile fatty acid (VFA) levels were always lower in reactors processing TFWWW (R2 and R4) and these values (< 400 mg/L, as acetic acid) were lower than the suggested limits for digester failure. The specific methanogenic activity (SMA) was twice as high in reactors R2 and R4 than in R1 and R3 after 120 days of operation when all reactors operated at an OLR of 20 g COD/L d.


Separate cortical and hippocampal cell populations target the rat nucleus reuniens and mammillary bodies.
Nucleus reuniens receives dense projections from both the hippocampus and the frontal cortices. Reflecting these connections, this nucleus is thought to enable executive functions, including those involving spatial learning. The mammillary bodies, which also support spatial learning, again receive dense hippocampal inputs, as well as lighter projections from medial frontal areas. The present study, therefore, compared the sources of these inputs to nucleus reuniens and the mammillary bodies. Retrograde tracer injections in rats showed how these two diencephalic sites receive projections from separate cell populations, often from adjacent layers in the same cortical areas. In the subiculum, which projects strongly to both sites, the mammillary body inputs originate from a homogenous pyramidal cell population in more superficial levels, while the cells that target nucleus reuniens most often originate from cells positioned at a deeper level. In these deeper levels, a more morphologically diverse set of subiculum cells contributes to the thalamic projection, especially at septal levels. While both diencephalic sites also receive medial frontal inputs, those to nucleus reuniens are especially dense. The densest inputs to the mammillary bodies appear to arise from the dorsal peduncular cortex, where the cells are mostly separate from deeper neurons that project to nucleus reuniens. Again, in those other cortical regions that innervate both nucleus reuniens and the mammillary bodies, there was no evidence of collateral projections. The findings support the notion that these diencephalic nuclei represent components of distinct, but complementary, systems that support different aspects of cognition.


What Drives Counter-Extremism? The Extent of P/CVE Policies in the West and Their Structural Correlates.
Counter-extremism (P/CVE) policies have shot to global prominence rapidly, yet there are large discrepancies in their implementation both between, and inside, countries. In this paper, we construct and present a robust index of P/CVE policies in Western countries (N = 38), based on data submitted by national experts, which we then use to test three hypothesized structural correlates of the extent of P/CVE implementation: threat of terrorism (measured as the number of past attacks/victims), size of Muslim minorities (Muslim communities have been "securitised" as potential threats in the post 9/11 period), and neoliberal governance (drawing on criminological literature that connects neoliberalism to anticipatory crime control). We find the first two structural factors to be positively and significantly correlated to the intensity of P/CVE deployment, while neoliberal governance negatively and significantly. In the discussion, we highlight the usefulness of a complementary in-depth qualitative research inspired by these findings.


Notch signaling induces rapid degradation of achaete-scute homolog 1.
In neural development, Notch signaling plays a key role in restricting neuronal differentiation, promoting the maintenance of progenitor cells. Classically, Notch signaling causes transactivation of Hairy-enhancer of Split (HES) genes which leads to transcriptional repression of neural determination and differentiation genes. We now report that in addition to its known transcriptional mechanism, Notch signaling also leads to rapid degradation of the basic helix-loop-helix (bHLH) transcription factor human achaete-scute homolog 1 (hASH1). Using recombinant adenoviruses expressing active Notch1 in small-cell lung cancer cells, we showed that the initial appearance of Notch1 coincided with the loss of hASH1 protein, preceding the full decay of hASH1 mRNA. Overexpression of HES1 alone was capable of down-regulating hASH1 mRNA but could not replicate the acute reduction of hASH1 protein induced by Notch1. When adenoviral hASH1 was coinfected with Notch1, we still observed a dramatic and abrupt loss of the exogenous hASH1 protein, despite high levels of ongoing hASH1 RNA expression. Notch1 treatment decreased the apparent half-life of the adenoviral hASH1 protein and increased the fraction of hASH1 which was polyubiquitinylated. The proteasome inhibitor MG132 reversed the Notch1-induced degradation. The Notch RAM domain was dispensable but a lack of the OPA and PEST domains inactivated this Notch1 action. Overexpression of the hASH1-dimerizing partner E12 could protect hASH1 from degradation. This novel function of activated Notch to rapidly degrade a class II bHLH protein may prove to be important in many contexts in development and in cancer.


Choosing the target wisely: partial tibial nerve transfer to extensor digitorum motor branches with simultaneous posterior tibial tendon transfer. Could this be a way to improve functional outcome and gait biomechanics?
The objective of this study was clinical assessment of the reduction of pathological motor phenomena with the recovery of long toe extensors, and evaluation of functional outcome with simultaneous nerve and tendon transfer in cases of common peroneal nerve (CPN) injuries. Seven male patients (mean age 26.4 years) received a partial tibial nerve transfer to the extensor hallucis longus muscle (MEHL) and extensor digitorum longus muscle (MEDL) motor branches, after a mean of 2.7 months following a traction-type injury to the CPN. Tibialis posterior muscle (MTP) tendon transfer through the interosseous route was performed on the same day. The follow-up period included a clinical neurological examination, a modified Stanmore System questionnaire (MSSQ), electromyographic examination of the interference pattern, and a video-based analysis of the gait biomechanics in the 3rd and 12th months. Video analysis of the gait investigated the presence or reduction of "stair-climbing maneuver" (SCM), foot slap (FS), and foot stability during the gait cycle. The average range of active dorsiflexion in the 3rd month was 0.85°. SCM accompanied walking in 6 patients (86%). FS accompanied walking in 3 patients (43%) and 3 patients (43%) avoided FS by planting the entire foot on the ground. All patients required orthopedic support (shoe inserts) to compensate for mediolateral foot instability. The average MSSQ score was 80.4 points. The average duration for the effective recovery of function (≥ 4 points on the Medical Research Council grading system) of long toe extensors was 11.2 months. The average range of active dorsiflexion in the 12th month increased to 4.4°. A reduction of FS was observed in 5 patients (71%). Excessive foot eversion was reduced in 4 patients (57%). Another 3 patients (43%) required no specific orthopedic shoe inserts. Reduction of pathological motor phenomena with recovery of the long toe extensors resulted in an increase of functional outcome. The average MSSQ score after 12 months was 92.4 points. Partial tibial nerve transfer to the motor branches of the extensor hallucis longus and the long toe extensors along with the simultaneous tibialis posterior tendon transfer produce the reduction of FS and bring mediolateral stability to the foot, i.e., improved gait biomechanics. The reduction of pathological motor phenomena at the time of recovery of the long toe extensors is reflected in an increase in patients' functional perception of the injured lower extremity during daily walking.


MicroRNA activity in the Arabidopsis male germline.
Most of the core proteins involved in the microRNA (miRNA) pathway in plants have been identified, and almost simultaneously hundreds of miRNA sequences processed in the Arabidopsis sporophyte have been discovered by exploiting next-generation sequencing technologies. However, there is very limited understanding about potentially distinct mechanisms of post-transcriptional regulation between different cell lineages. In this review the focus is on the Arabidopsis male gametophyte (pollen), where the germline differentiates after meiosis giving rise to the male gametes. Based on comparative analysis of miRNAs identified in sperm cells by in-depth sequencing, their possible functions during germ cell specification and beyond fertilization are discussed. In addition, 25 potentially novel miRNAs processed in sperm cells and pollen were identified, as well as enriched variations in the sequence length of known miRNAs, which might indicate subfunctionalization by association with a putative germline-specific Argonaute complex. ARGONAUTE 5 (AGO5), by close homology to AGO1 and localizing preferentially to the sperm cell cytoplasm in mature pollen, may be part of such a complex.


Weighted Burgers Vector analysis of orientation fields from high-angular resolution electron backscatter diffraction.
The Weighted Burgers Vector (WBV) method can extract information about dislocation types and densities present in distorted crystalline materials from electron backscatter diffraction (EBSD) maps, using no assumptions about which slip systems might be present. Furthermore, high-angular resolution EBSD (HR-EBSD) uses a cross-correlation procedure to increase the angular precision of EBSD measurements by an order of magnitude compared to conventional EBSD. However, the WBV technique has not previously been applied to HR-EBSD data and therefore it remains unclear as to which low-angle substructures can be reliably characterised by WBV analysis of conventional EBSD data and which require additional HR-EBSD processing. To establish some practical examples that can be used to guide future data-acquisition strategies, we compare the output of the WBV method when applied to conventional EBSD data and HR-EBSD data collected from the most common minerals in Earth's lower crust (plagioclase feldspar) and upper mantle (olivine). The results demonstrate that HR-EBSD and WBV processing are complementary techniques. The increase in angular precision achieved with HR-EBSD processing allows low-angle (on the order of 0.1°) structures, which are obscured by noise in conventional EBSD data, to be analyzed quantitatively using the WBV method. Combining the WBV and HR-EBSD methods increases the precision of calculated WBV directions, which is essential when using information about active slip systems to infer likely deformation mechanisms from naturally deformed microstructures. This increase in precision is particularly important for low-symmetry crystals, such as plagioclase, that have a wide range of available slip systems that vary in relative activity with changing pressure, temperature and differential stress. Because WBV directions are calculated using no assumptions about which slip systems may be present, combining this technique with HR-EBSD to refine the precision of lattice orientation gradients is ideal for investigating complex natural materials with unknown deformation histories.


Modified splitting technique for liver transplantation in adult-sized recipients. Technique and preliminary results.
In the common split liver technique the liver is divided between the right lobe, to be transplanted to an adult, and the left lateral segment, to be transplanted to a small child. We have developed an alternative technique by which the cadaver donor liver is divided in its two anatomo-functional halves, both apt to be transplanted to adults or children of adult size. We have so far used this technique in three multi organ donors, generating, six liver grafts that we transplanted to six recipients with median age of 36.5 years (range 10-23) and a median weight of 55 kg (range 38-79). Patient survival was 83.3% and graft survival 66.6% with a median follow up of 10 months (range 8-14). These results show that the technique is effective and that it can consistently increase the number of liver grafts that can be transplanted into adult patients, with the available cadaver donor pool.


Practice facilitation to implement alcohol-related care in Veterans Health Administration liver clinics: a study protocol.
Alcohol-related care, including screening, brief intervention, and provision of/referral to medication or behavioral treatments for alcohol use disorder, could be delivered in liver clinics to better reach patients with chronic liver conditions. However, the provision of alcohol-related care in liver clinics is currently suboptimal. Practice facilitation is an evidence-based implementation strategy that may address barriers, harness facilitators, and optimize the implementation of alcohol-related care in liver clinic settings using a clinic-centered approach. We report the protocol of a study to test a practice facilitation intervention to implement alcohol-related care in four Veterans Health Administration liver clinics. This study will employ a Hybrid Type 3 effectiveness-implementation design, in which implementation outcomes are considered primary and clinical outcomes secondary. Intervention and evaluation design were informed by the Consolidated Framework for Implementation Research. Qualitative data collected from clinical stakeholders and patients were used to tailor the intervention. The intervention involves a 6-month period of external practice facilitation, including regular meetings to identify clinic goals, challenges, and solutions; engagement of clinic champions; provision of training and development of educational materials for clinic staff and patients; and performance monitoring and feedback. Ongoing formative evaluation involves the collection of quantitative facilitator tracking data and qualitative data from meeting notes and patient interviews to describe intervention acceptability, feasibility, and adoption, and adjust implementation as needed. In the summative evaluation, implementation outcomes (clinic rates of screening, brief intervention, and treatment referral/receipt) and clinical outcomes (unhealthy alcohol use, liver health) will be assessed among patients in participating clinics using secondary electronic health record data and interrupted time series analysis. This will be the first study to our knowledge to test practice facilitation to implement alcohol-related care in liver clinic settings. Results from formative and summative evaluation will inform a framework for the successful implementation of effective alcohol-related care through practice facilitation in liver clinics, which may ultimately lead to better health outcomes for patients with chronic liver disease.