Effectiveness of seasonal inactivated influenza vaccination in Japanese schoolchildren: an epidemiologic study at the community level.
Influenza vaccination is the most effective method for preventing influenza virus infection. The incidence of influenza is higher in schoolchildren than other age groups. This study evaluated the effectiveness of seasonal inactivated influenza vaccination (IIV) in a community population of schoolchildren during two seasons. This study was a cross-sectional survey of public schoolchildren based on data collected in the 2012/2013 and 2014/2015 seasons. The questionnaire was distributed to all public schoolchildren of target grade in a survey area, and 7945 respondents were included in the analysis. The vaccination status and influenza onset were defined based on the self-reported questionnaire by parents or guardians. Generalized linear mixed models were used to adjust clustering within schools and individual covariates and calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between vaccination status and influenza onset. The influenza incidence was higher in the 2015 than the 2013 survey (25% versus 17%), although the vaccination rates were comparable between the two seasons. Receiving one- or two-dose vaccination was more protective against influenza than non-vaccination in both the 2013 (OR, 0.77; 95%CI, 0.65-0.92) and 2015 (OR, 0.88; 95%CI, 0.75-1.02) surveys. Full vaccination was also more protective in both the 2013 (OR, 0.75; 95%CI, 0.62-0.89) and 2015 (OR, 0.86; 95%CI, 0.74-1.00) surveys. Seasonal IIV was protective against influenza for Japanese schoolchildren in a community-based real-world setting. The difference in clinical effectiveness of IIV between the two seasons was likely due to the antigenic mismatch between the circulating and vaccine strains.


[Phasic activity of REM sleep in newborns and infants and its relationship with apnea episodes].
When the apnea hypothesis turned to be an explanation for sudden infant death syndrome (SIDS) many authors tried to find if near-miss or apparent life-threatening events (ALTE) could be markers of SIDS. It was suggested that phasic REM activity is associated with increased respiratory neuron activity and prevents prolonged apnea in near-miss SIDS. In a previous retrospective study with newborns we did not confirm these results, nevertheless we had several babies with serious neurological disturbances. The aim of this study was to verify the relationship of phasic activity (rapid eyes movement and sucking bursts) with both apneic and non-apneic epochs during REM sleep. We studied 86 children referred for evaluation because they presented an ALTE during sleep or apneas. The subjects were divided in three groups by age (newborns, n = 31; 1-6 months, n = 48; and > 6 < 12 months, n = 7). They were all submitted to a clinical and neurological evaluation in order to detect possible etiological factors to the apneic episode. The polysomnograms (PS) consisted of EEG, submental EMG, electro-oculogram and cardiorespiratory monitoring. The records were made between 11 am and 15 pm for 2 or 3 hours. The electrodes were disposed in the 10-20 system. During one five-minutes epoch of REM sleep we verified the incidence of phasic activity (rapid eyes movement or sucking bursts) time locked to apneic episodes and compared with a similar duration non-apneic epoch. To evaluate the relationship of phasic activity with apneic and non-apneic eopchs we compared the incidence of rapid eyes movements and sucking bursts in each group. Our results showed that phasic activity of REM sleep (sucking bursts) seems to be more frequent in newborns in non-apneic epochs (p < 0.05). Between 1-6 months the number of rapid eyes movements were more frequent in non-apneic epochs (p = 0.001). In conclusion our findings suggest that phasic activity of REM sleep seems to be more evident in nonapneic epochs during the first six months of life. Although central apneas may have their origin in an intrinsic disturb of the respiratory control center they may be influenced by the phasic activity of REM sleep. The rapid eyes movements and sucking bursts may have a protection effect against apneas at least in the first 6 months of life. which is the predominant period for SIDS. We suggest that the excitatory driving related to generation of phasic activity in REM sleep may block or atenuate tonic inhibition of respiratory motoneuron and avoid apnea. It is still open for discussion the possible relation between failure of this protective mechanism and SIDS.


Quantum reality with negative-mass particles.
Physical interpretations of the time-symmetric formulation of quantum mechanics, due to Aharonov, Bergmann, and Lebowitz are discussed in terms of weak values. The most direct, yet somewhat naive, interpretation uses the time-symmetric formulation to assign eigenvalues to unmeasured observables of a system, which results in logical paradoxes, and no clear physical picture. A top-down ontological model is introduced that treats the weak values of observables as physically real during the time between pre- and post-selection (PPS), which avoids these paradoxes. The generally delocalized rank-1 projectors of a quantum system describe its fundamental ontological elements, and the highest-rank projectors corresponding to individual localized objects describe an emergent particle model, with unusual particles, whose masses and energies may be negative or imaginary. This retrocausal top-down model leads to an intuitive particle-based ontological picture, wherein weak measurements directly probe the properties of these exotic particles, which exist whether or not they are actually measured.


The transcription factor Sp1 modulates RNA polymerase III gene transcription by controlling BRF1 and GTF3C2 expression in human cells.
Specificity protein 1 (Sp1) is an important transcription factor implicated in numerous cellular processes. However, whether Sp1 is involved in the regulation of RNA polymerase III (Pol III)-directed gene transcription in human cells remains unknown. Here, we first show that filamin A (FLNA) represses Sp1 expression as well as expression of TFIIB-related factor 1 (BRF1) and general transcription factor III C subunit 2 (GTF3C2) in HeLa, 293T, and SaOS2 cell lines stably expressing FLNA-silencing shRNAs. Both BRF1 promoter 4 (BRF1P4) and GTF3C2 promoter 2 (GTF3C2P2) contain putative Sp1-binding sites, suggesting that Sp1 affects Pol III gene transcription by regulating BRF1 and GTF3C2 expression. We demonstrate that Sp1 knockdown inhibits Pol III gene transcription, BRF1 and GTF3C2 expression, and the proliferation of 293T and HeLa cells, whereas Sp1 overexpression enhances these activities. We obtained a comparable result in a cell line in which both FLNA and Sp1 were depleted. These results indicate that Sp1 is involved in the regulation of Pol III gene transcription independently of FLNA expression. Reporter gene assays showed that alteration of Sp1 expression affects BRF1P4 and GTF3C2P2 activation, suggesting that Sp1 modulates Pol III-mediated gene transcription by controlling BRF1 and GTF3C2 gene expression. Further analysis revealed that Sp1 interacts with and thereby promotes the occupancies of TATA box-binding protein, TFIIAα, and p300 at both BRF1P4 and GTF3C2P2. These findings indicate that Sp1 controls Pol III-directed transcription and shed light on how Sp1 regulates cancer cell proliferation.


[Diabetes mellitus caused by pancreatitis in a bull].
This paper describes a 6-year-old Simmental bull with diabetes mellitus. The animal was referred to our clinic because of severe weight loss and chronic indigestion. Clinical examination revealed markedly disturbed general condition, impaired forestomach function and polyuria. There was aciduria, glucosuria and ketonuria. The most important biochemical findings were severe hyperglycemia, markedly increased activities of hepatic enzymes and severe metabolic acidosis. Plasma concentrations of insulin, insulin-like growth factor-I, thyroxine and 3,5,3'-triiodothyronine were lower than normal, whereas those of glucagon were higher than normal. Based on these findings, a diagnosis (secondary) diabetes mellitus was made. The bull was slaughtered and histological examination revealed mixed cell pancreatitis with severe degeneration of islet cells. Immunohistochemical examination of the pancreas showed that very few insulin-, glucagon-, somatostatin- and pancreatic polypeptide, insulin-like growth factor-I and adrenomedullin-producing islet cells were present.


Half-sized cylindrical invisibility cloaks using double near zero slabs with realistic material size and properties.
A method is introduced to miniaturize invisibility cloaks by 50% using wave tailoring and finite/non-zero wave impedance of double near zero (DNZ) slabs. Unlike previous works, which use thick dielectric matching layers to miniaturize internal cloaks, the proposed technique is applied to both internal and external cylindrical cloaks using a thin and short DNZ slab to change cloaks' shapes to half-cylinder shells. Moreover, sets of structures are introduced for the half sized cloaks to enable using feasible-to-fabricate structures with the help of a rigorous theoretical analysis, which is validated via full-wave simulations. All of the presented results show that the proposed half cloaks can function perfectly well. The sensitivity of half-sized cloaks to the length and material properties of the DNZ slab is investigated to find the shortest length and the highest values of the permittivity and permeability for the slab to have small yet realizable structures. The analysis shows that slabs with length as small as the diameter of the cloaks and constitutive parameters (permittivity and permeability) as high asεslab=μslab=0.1-0.1iand εslab=μslab=0.05-0.04i for half-sized external cloaks and half-sized internal cloaks, respectively, can still considerably reduce the scattered fields. The effect of the loss and incident angle of the field on the performance of the miniaturized cloaks are also analyzed.


The Emerging Potential of Advanced Targeted Mass Spectrometry to Become a Routine Tool for Protein Quantification in Biomedical Research.
Mass spectrometry-based proteomics has become an indispensable tool for system-wide protein quantification in systems biology, biomedical research, and increasing for clinical applications. In particular, targeted mass spectrometry offers the most sensitive and reproducible quantitative detection of proteins, peptides and post-translational modifications of any currently applied mass spectrometry technique and is therefore ideally suited to generate high quality quantitative datasets. Despite these apparent advantages, targeted mass spectrometry is only slowly gaining popularity in academia and pharmaceutical industries, mainly due to the additional efforts in assay generation and manual data validation. However, with the increasing accumulation of mass spectrometry data, advances in deep learning spectral prediction for automated assay development, these obstacles can and will be considerably reduced in the near future. Here, we describe the latest technological developments in this field and discuss the emerging importance of targeted mass spectrometry for systems biology research and potential key roles in bridging biomedical discovery and clinical implementation.


Graphene-based wireless bacteria detection on tooth enamel.
Direct interfacing of nanosensors onto biomaterials could impact health quality monitoring and adaptive threat detection. Graphene is capable of highly sensitive analyte detection due to its nanoscale nature. Here we show that graphene can be printed onto water-soluble silk. This in turn permits intimate biotransfer of graphene nanosensors onto biomaterials, including tooth enamel. The result is a fully biointerfaced sensing platform, which can be tuned to detect target analytes. For example, via self-assembly of antimicrobial peptides onto graphene, we show bioselective detection of bacteria at single-cell levels. Incorporation of a resonant coil eliminates the need for onboard power and external connections. Combining these elements yields two-tiered interfacing of peptide-graphene nanosensors with biomaterials. In particular, we demonstrate integration onto a tooth for remote monitoring of respiration and bacteria detection in saliva. Overall, this strategy of interfacing graphene nanosensors with biomaterials represents a versatile approach for ubiquitous detection of biochemical targets.


Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role.
Higher TSH values, even within normal ranges, have been associated with a greater risk of thyroid malignancy. The relationship between TSH and papillary thyroid cancer (PTC) has been analyzed in 10 178 patients submitted to fine needle aspiration of thyroid nodules with a cytology of PTC (n=497) or benign thyroid nodular disease (BTND, n=9681). In 942 patients, submitted to surgery (521 from BTND and 421 from PTC), the histological diagnosis confirmed an elevated specificity (99.6%) and sensitivity (98.1%) of cytology. TSH levels were significantly higher in PTC than in BTND both in the cytological and histological series and also in patients with a clinical diagnosis of multinodular goiter (MNG) and single/isolate nodule (S/I). A significant age-dependent development of thyroid autonomy (TSH <0.4 microU/ml) was observed in patients with benign thyroid disease, but not in those with PTC, diagnosed both on cytology and histology. In patients with MNG, the frequency of thyroid autonomy was higher and the risk of PTC was lower compared to those with S/I. In all patients, the presence of thyroid auto-antibodies (TAb) was associated with a significant increase of TSH. However, both in TAb positive and TAb negative patients TSH levels were significantly higher in PTC than in BTND. Our data confirm a direct relationship between TSH levels and risk of PTC in patients with nodular thyroid diseases. Thyroid autonomy conceivably protects against the risk of PTC, while thyroid autoimmunity does not play a significant role.


Agreement between two methods for retrospective assessment of occupational exposure intensity to six chlorinated solvents: Data from The National Birth Defects Prevention Study.
The wide variety of jobs encountered in population-based studies makes retrospective exposure assessment challenging in occupational epidemiology. In this analysis, two methods for estimating exposure intensity to chlorinated solvents are compared: rated (assigned by an expert rater) and modeled (assigned using statistical models). Estimates of rated and modeled intensities were compared for jobs held by mothers participating in the National Birth Defects Prevention Study with possible exposure to six chlorinated solvents: carbon tetrachloride, chloroform, methylene chloride, perchloroethylene, 1,1,1-trichloroethane, and trichloroethylene. For each possibly exposed job, an industrial hygienist assigned (1) an exposure intensity (rated intensity) and (2) determinants of exposure to be used in a statistical model of exposure intensity (modeled intensity). Of 12,326 reported jobs, between 31 (0.3%) and 746 (6%) jobs were rated as possibly exposed to each of the six solvents. Agreement between rated and modeled intensities was low overall (Spearman correlation coefficient range: -0.09 to 0.28; kappa range: -0.23 to 0.43). Although no air measurements were available to determine if rated or modeled estimates were more accurate, review of participants' job titles showed that modeled estimates were often unexpectedly high given the low-exposure tasks found in these jobs. Differences between the high-exposure jobs used to create the statistical models (obtained from air measurements in the published literature) and the low-exposure jobs in the actual study population is a potential explanation for the disagreement between the two methods. Investigators should be aware that statistical models estimating exposure intensity using existing data from one type of worker population might not be generalizable to all populations of workers.


Oxygen-stable hemolysins of group A streptococci. 8. Leukotoxic and antiphagocytic effects of streptolysins S and O.
Streptolysin S exists in a cell-bound form and as an extracellular complex between a nonspecific carrier (serum, serum albumin, ribonucleic acid [RNA], Triton, Tween) and a hemolytic moiety (probably a peptide) synthesized by streptococci. Although all the forms of streptolysin S, at 100 hemolytic units, killed mouse leukocyte monolayers, the time needed to kill 100% of the cells varied with the different streptolysin S preparations. Whereas 30 min was sufficient for the cell-bound hemolysin to kill all of the cells, 60 and 180 min were required when RNA streptolysin S and serum streptolysin S, respectively, were employed. Addition of 10% mouse serum to RNA streptolysin S or to cell-bound hemolysin delayed the killing of the leukocytes. The delayed killing observed with serum and albumin hemolysins is probably due to competition for the hemolytic moiety between the carrier molecules and target sites (phospholipids) upon the leukocyte membrane. Serum streptolysin S must be constantly incubated with the cells for 90 min for 100% of the cells to undergo cytopathic changes upon subsequent incubation for an additional 90 min. Streptolysin S inhibitor (trypan blue) added to the system after 30 or 60 min of incubation resulted in the killing of 50 and 100% of the leukocytes, respectively, when the cells were further incubated for 120 min. It is suggested that 30 min of incubation was not sufficient for the transfer of enough streptolysin S molecules upon the cell surface to allow killing of all of the cells. Sublethal amounts of streptolysin S, streptolysin O, and saponin suppressed phagocytosis of streptococci by mouse peritoneal macrophages. This effect was abolished by inhibitors of streptolysin S (trypan blue) and of streptolysin O and saponin (cholesterol). With sublethal amounts of streptolysin S, no inhibition of the reduction of nitro blue tetrazolium by nonphagocytosing cells was observed, but these amounts of streptolysin S caused a 50% inhibition of the reduction of nitro blue tetrazolium by phagocytosing leukocytes. It is suggested that some metabolic systems, which are normally enhanced during phagocytosis, have been affected by sublethal doses of streptolysin S. The results indicate that the in vivo production of small amounts of streptolysins S and O by group A streptococci may inhibit phagocytosis and may thus contribute to the invasiveness and pathogenicity of this microorganism.


Use of low level laser therapy to control neuropathic pain: A systematic review.
Neuropathic pain can be defined as pain initiated or caused by a primary lesion or dysfunction in the central or peripheral nervous system. The low level laser therapy (LLLT) has gained great prominence as a treatment in this type of pain; however, the application parameters are still controversial in the literature. This study aimed to review the literature on the use of LLLT in neuropathic pain with the goal of establishing a "therapeutic window" for the effective use of this treatment. We analyzed 14 articles, 10 in experimental animals and 4 in humans. The results are presented in three tables, the first being for comparison of the studies' application parameters, the second showing the average and median parameters experimental studies and third showing the clinical studies embodiment. The experimental studies revealed better results for LLLT and infrared laser powers above 70mW. Clinical studies are inconclusive as to the application parameters, due to the discrepancy; however all demonstrate the effectiveness of LLLT. According to the data presented, it was concluded that LLLT has positive effects on the control of analgesia for neuropathic pain, but further studies with high scientific rigor are needed in order to define treatment protocols that optimize the action LLLT in neuropathic pain.


Profiling the perceptual suppression of partials in periodic complex tones: further evidence for a harmonic template.
The basis for the perceptual cohesion of periodic complex tones was investigated. In experiment 1, 2-4 consecutive components (harmonics 6 and above) were removed from a 14-harmonic complex and replaced with a sinusoidal "probe," located at one of a set of regularly spaced positions spanning the gap. On each trial, subjects heard a complex tone followed by an adjustable pure tone in a continuous loop. Subjects were better able to match the pure tone to the probe when the probe did not coincide with a harmonic position. Minima in "hit rate" were more pronounced when harmonic probes were in positions adjacent to other harmonics than when they were not. These findings suggest that the pitch of each in-tune partial was actively suppressed by a template whose influence attenuated with distance from regions of consecutive harmonics. In experiment 2, the partials on either side of the spectral gap were harmonics of different fundamental frequencies. Hit-rate minima corresponding to both fundamentals were found, indicating an upward and downward spread of suppression, and also demonstrating the concurrent operation of two templates. The results confirm recent findings in support of template models, and are consistent with the idea that partial-pitch suppression underpins harmonic fusion.


Climate-related environmental variation in a visual signalling device: the male and female dewlap in Anolis sagrei lizards.
Animals communicate using a variety of signals that differ dramatically among and within species. The astonishing dewlap diversity in anoles has attracted considerable attention in this respect. Yet, the evolutionary processes behind it remain elusive and have mostly been explored for males only. Here, we considered Anolis sagrei males and females to study signal divergence among populations. First, we assessed the degree of variation in dewlap design (size, pattern and colour) and displays by comparing 17 populations distributed across the Caribbean. Second, we assessed whether the observed dewlap diversity is associated with variation in climate-related environmental conditions. Results showed that populations differed in all dewlap characteristics, with the exception of display rate in females. We further found that males and females occurring in 'xeric' environments had a higher proportion of solid dewlaps with higher UV reflectance. In addition, lizards inhabiting 'mesic' environments had primarily marginal dewlaps showing high reflectance in red. For dewlap display, a correlation with environment was only observed in males. Our study provides evidence for a strong relationship between signal design and prevailing environmental conditions, which may result from differential selection on signal efficacy. Moreover, our study highlights the importance of including females when studying dewlaps in an evolutionary context.


Extraintestinal manifestations of Crohn's disease.
In each case of extraintestinal manifestations of Crohn's disease, active disease, if present, should be treated to induce remission, which may positively influence the course of most concomitant extraintestinal manifestations. For some extraintestinal manifestations, however, a specific treatment should be introduced. This latter part of disease management will be discussed in this chapter, in particular for pyoderma gangrenosum, uveitis, spondylarthropathy--axial arthropathy--and primarysclerosing cholangitis, which have also been described in quiescent Crohn's disease. Few new drugs for the treatment of extraintestinal manifestations of Crohn's disease have been developed in the past and only the role of infliximab has increased in Crohn's disease-related extraintestinal manifestations. Drugs specifically aimed at this treatment, stemming from a few randomized controlled studies or case series, are sulfasalazine, 5-ASA, corticosteroids, azathioprine or 6-mercaptopurine, methotrexate, infliximab, dapsone and cyclosporine or tacrolimus.


Surgically increased ovarian mass in the honey bee confirms link between reproductive physiology and worker behavior.
Honey bee (Apis mellifera L.) workers are essentially sterile females that are used to study how complex social behavior develops. Workers perform nest tasks, like nursing larvae, prior to field tasks, like foraging. Despite worker sterility, this behavioral progression correlates with ovary size: workers with larger ovaries (many ovary filaments) start foraging at younger ages on average. It is untested, however, whether the correlation confers a causal relationship between ovary size and behavioral development. Here, we successfully grafted supernumerary ovaries into worker bees to produce an artificial increase in the amount of ovary tissue. We next measured fat body mRNA levels for the yolk precursor gene vitellogenin, which influences honey bee behavioral development and can correlate with ovary size. Vitellogenin was equally expressed in surgical controls and bees with supernumerary ovaries, leading us to predict that these groups would be characterized by equal behavior. Contrary to our prediction, bees with supernumerary ovaries showed accelerated behavioral development compared to surgical controls, which behaved like reference bees that were not treated surgically. To explore this result we monitored fat body expression levels of a putative ecdysteroid-response gene, HR46, which is genetically linked to ovary size in workers. Our data establish that social insect worker behavior can be directly influenced by ovaries, and that HR46 expression changes with ovary size independent of vitellogenin.


Safety assessment of petrochemical enterprise using the cloud model, PHA-LOPA and the bow-tie model.
Safe production is the foundation of the normal operations of petrochemical enterprises, and it helps maintain social stability. The main purpose of this study is to prevent petrochemical enterprise accidents by proposing a composite safety assessment approach based on the cloud model, preliminary hazard analysis-layer of protection analysis (PHA-LOPA) and the bow-tie model. First, the petrochemical enterprise and its relevant indicators were evaluated based on the cloud model. Second, the quantitative effect of the uncertainty transformation on the evaluation result of the cloud model was further analysed. This mainly includes the error analysis of the numerical characteristics under the conditions of few samples and small values. Third, the critical indicators such as shock and noise can be weakened and prevented by corresponding safety measures based on PHA-LOPA and the bow-tie model. After adopting two independent protection layers, the risk levels of shock and noise decrease from 3 to 2. Then, shock and noise were analysed in depth with the bow-tie model, and the causes and consequences were identified. Moreover, corresponding safety measures were taken to prevent accidents. The case study validated the validity and feasibility of the composite safety assessment approach proposed here.


Variations in the mechanical properties of cartilage from the canine scapulohumeral joint.
To measure the intrinsic material properties of scapulohumeral joint cartilage in adult dogs and determine whether regional differences exist within or between the humeral and glenoid cartilages. Paired shoulder joints from 7 clinically normal adult dogs. An automated indentation apparatus was used to obtain the intrinsic mechanical properties of the cartilage at 7 sites on each joint surface. Topographic variations in mechanical properties of the glenoid and humeral cartilages were observed. The largest aggregate modulus (HA) for the humerus was seen at the caudocentral site (0.92 MPa) and for the scapula was seen at the centrocenter site (0.84 MPa). The mean shear modulus (mu) of humeral cartilage (0.23 MPa) was significantly greater than that of the glenoid cartilage (0.19 MPa). The mean Poisson's ratio (v) of humeral cartilage (0.24) was significantly smaller than that for the glenoid cartilage (0.29). Mean humeral cartilage aggregate modulus (0.71 MPa) was larger than the value for glenoid cartilage (0.67 MPa), but these differences were not significant. There were no significant differences in the compressive stiffness of the opposing cartilage in the canine scapulohumeral joint. Differences in mechanical properties between opposing humeral and glenoid cartilages are not a cause of cartilage injury in the scapulohumeral joint of adult dogs. The mechanical properties of cartilage from young dogs with open physes and incomplete subchondral bone plates may be different from those of adult dogs.


Genetics of plasma cholesterol and triglycerides: a study of adult male twins.
Fasting plasma triglycerides and cholesterol, as well as cholesterol in very low density, low density and high density lipoproteins, were measured in 250 MZ and 264 DZ adult male twin pairs. A new method was used to choose an estimate of genetic variance. This includes an estimate of genetic variance for use when the total variances of MZ and DZ twins are unequal. DZ twins had greater total variance for cholesterol. When genetic variance was estimated by subtracting the within-MZ-sets mean square from the within-DZ-sets mean square, all of the lipids had significant estimates of genetic variance; however, when genetic variance was estimated by a method designed to correct bias due to unequal total variances of MZ and DZ twins, only triglycerides had significant genetic variance. The heritability of plasma triglycerides was calculated to be 0.68.


Stereochemical promiscuity in artificial transcriptional activators.
Small molecule replacements of transcriptional activation domains are highly desirable targets due to their utility as mechanistic tools and their long-term therapeutic potential for a variety of human diseases. Here, we examine the ability of amphipathic isoxazolidines differing only in the placement of constituent side chains to function as transcriptional activation domains. The results reveal that precise positioning of functional groups within a conformationally constrained small molecule scaffold is not required for transcription function; rather, the balance of polarity and hydrophobicity within the scaffold is the more important determinant of transcription function. This suggests that a number of different organic molecule scaffolds should function as transcriptional activator domains when appropriately functionalized, a hypothesis currently under investigation.


Pentobarbital suppresses basal and reflexive pancreatic polypeptide release in dogs.
We sought to determine in overnight-fasted dogs whether basal or 2-deoxy-D-glucose (2-DG)-stimulated levels of pancreatic polypeptide (PP) could be reliably used as an index of cholinergic activity at the pancreas and thereby determine the effect of pentobarbital anesthesia on this cholinergic outflow. At low basal PP levels, either atropine or pentobarbital had a small effect on PP levels; at higher basal levels, both atropine and pentobarbital had a larger effect. Thus both drugs decreased PP in proportion to its initial basal level, suggesting that basal PP levels have a variable cholinergic component. Atropine abolished the PP response to intravenous 2-DG, confirming in our animal model that the PP response to neuroglucopenia is entirely cholinergically mediated. Pentobarbital also abolished the PP response to 2-DG, suggesting that anesthesia either suppresses cholinergic outflow to the pancreas or the response of the pancreatic F-cell to it. To test the latter hypothesis, the acetylcholine analogue bethanechol was administered before and during pentobarbital anesthesia. The PP response to direct cholinergic stimulation was not abolished by pentobarbital, although it was reduced modestly. We conclude that only part of the basal level of PP is under cholinergic control; all of the PP response to 2-DG is cholinergically mediated; pentobarbital anesthesia abolishes the cholinergic input to the pancreas; and if the endogenous cholinergic input influences certain pancreatic endocrine and exocrine responses, then its contribution would be seriously underestimated when studied in pentobarbital-anesthetized animals.


Fasudil, a Rho-kinase inhibitor, attenuates glomerulosclerosis in Dahl salt-sensitive rats.
The present study was designed to clarify whether the Rho-Rho-kinase pathway is involved in the process of hypertensive glomerulosclerosis and to assess the therapeutic effect of fasudil, a specific Rho-kinase inhibitor. Dahl salt-sensitive rats (DS) and Dahl salt-resistant rats (DR) were fed a high-salt diet at 6 weeks of age. Fasudil (30 mg/kg per day) was administered for 7 weeks to DS starting at the age of 11 weeks. After 7 weeks, untreated DS were characterized by decreased kidney function, increased proteinuria, abnormal morphological findings, increased adrenomedullin and atrial natriuretic peptide (ANP) levels, and increased renal messenger RNA expression of RhoB, Rho-kinasealpha, Rho-kinasebeta, collagen I and collagen III, and transforming growth factor-beta (TGF-beta) in the renal cortex compared with DR. Chronic fasudil treatment significantly improved renal function (serum creatinine, -26%; blood urea nitrogen, -41%; creatinine clearance, +42%), proteinuria (-24%) and histological findings (glomerular injury score, -49%; afferent arteriolar injury score, -17%) without changing blood pressure compared with untreated DS. Interestingly, long-term fasudil treatment decreased the plasma adrenomedullin (-25%) and ANP (-49%), but did not change the plasma renin or aldosterone. Furthermore, fasudil significantly decreased the messenger RNA expression of TGF-beta (-20%), collagen I (-23%), and collagen III (-24%) in the renal cortex. However, there were still significant differences in the aforementioned parameters between DR and fasudil-treated DS. These results suggest that the Rho-Rho-kinase pathway may be partly responsible for the pathogenesis of hypertensive glomerulosclerosis independently of blood pressure in DS, and that chronic inhibition of the Rho-Rho-kinase pathway may be a new strategy for treating hypertensive nephrosclerosis.


Ornithine metabolism in male and female rat kidney: mitochondrial expression of ornithine aminotransferase and arginase II.
In the kidney, L-ornithine is reabsorbed along the proximal convoluted tubule (PCT), transported by basolateral carriers, and produced by arginase II (AII). Here, the renal metabolic fate of L-ornithine was analyzed in male and female rats. Kidneys and renal zones were dissected and used for Western blot analysis, immunofluorescence, and electron microscopic studies. Ornithine aminotransferase (OAT) and AII were localized using specific antibodies. Ornithine oxidation was determined by incubating microdissected tubules with L-[1-14C] or L-[U-14C]ornithine in the presence or absence of energy-providing substrates. Ornithine decarboxylase (ODC) mRNAs were localized by in situ hybridization. The 48-kDa OAT protein was detected in male and female kidneys, but its level was fourfold higher in the latter. OAT relative distribution increased from the superficial cortex toward the outer medulla to reach its highest level. Almost all OAT protein was localized in cortical and medullary proximal straight tubules (CPST and OSPST, respectively). In proximal straight tubule (PST), AII protein distribution overlapped that of OAT. No gender difference in AII protein level was found. OAT and AII were colocalized within PST mitochondria. L-[1-14C]ornithine decarboxylation occurred in all tubules, but predominantly in proximal tubules. L-[1-14C]ornithine decarboxylation was enhanced when L-[1-14C]ornithine was given to tubules as the sole substrate. The use of L-[U-14C]ornithine demonstrated the complete oxidation of ornithine. In conclusion, the OAT gene was expressed more in female rat proximal tubules than in male. Because OAT and AII proteins overlapped in PST mitochondria, L-arginine-derived ornithine may be preferentially converted to L-glutamate, as proven by ornithine oxidation. However, the coexpression of ODC, glutamate decarboxylase, and glutamine synthetase in PST suggests that L-ornithine can also be metabolized to putrescine, GABA, and L-glutamine. The fate of L-ornithine may depend on the cellular context.


Bone marrow cell transplants involving intra-H-2 recombinant inbred mouse strains. Evidence that hemopoietic histocompatibility-1 (Hh-1) genes are distinct from H-2D or H-2L.
Hemopoietic histocompatibility (Hh) Ag are noncodominantly expressed on bone marrow stem cells and other normal and neoplastic cells of hemopoietic origin. H-2/Hh-1 allogeneic or parental-strain bone marrow grafts are eliminated in a determinant specific manner by NK cells. In inbred mouse strains, seven Hh-1 alleles representing combinations of five different Hh-1 antigenic determinants are described. Each Hh-1 allele maps in the vicinity of H-2D, and the genes that map to Hh-1 are transacting regulatory genes. The expression of a particular determinant depends on the absence of the regulatory gene and the presence of the appropriate structural gene. The primary focus of this study is to ascertain whether the Hh-1 phenotype and the serologic H-2DL typing are always correlated or whether recombinant can separate the two. To achieve this, we used a panel of irradiated hosts that are able to recognize the different Hh-1 determinants on the bone marrow cells of congenic intra-H-2 recombinant donors. We report: 1) the majority of strains show a correlation between Hh-1 and H-2DL: 2) B10.RQDB and B10.WB strains dissociate Hh-1 from Lb: 3) nine H-2S/D interval recombinant strains exhibit no correlation between the H-2DL type and Hh-1 phenotype; and 4) in two strains from this group, B10.D2 (R106) and B10.RSF5, H-2S/D crossovers occurred within Hh-1r, (Hh-1 regulatory). We conclude that Hh-1r is a distinct regulatory locus mapping telomeric of H-2S and centromeric of, although probably closer to, H-2D.


Divalent Metal Ion Activation of a Guanine General Base in the Hammerhead Ribozyme: Insights from Molecular Simulations.
The hammerhead ribozyme is a well-studied nucleolytic ribozyme that catalyzes the self-cleavage of the RNA phosphodiester backbone. Despite experimental and theoretical efforts, key questions remain about details of the mechanism with regard to the activation of the nucleophile by the putative general base guanine (G12). Straightforward interpretation of the measured activity-pH data implies the pKa value of the N1 position in the G12 nucleobase is significantly shifted by the ribozyme environment. Recent crystallographic and biochemical work has identified pH-dependent divalent metal ion binding at the N7/O6 position of G12, leading to the hypothesis that this binding mode could induce a pKa shift of G12 toward neutrality. We present computational results that support this hypothesis and provide a model that unifies the interpretation of available structural and biochemical data and paints a detailed mechanistic picture of the general base step of the reaction. Experimentally testable predictions are made for mutational and rescue effects on G12, which will give further insights into the catalytic mechanism. These results contribute to our growing knowledge of the potential roles of divalent metal ions in RNA catalysis.


Birth intervals and injectable contraception in sub-Saharan Africa.
The interval between births is associated with child survival in the developing world. We aimed to investigate associations between use of depot-medroxyprogesterone acetate and other reversible contraception and short birth intervals in sub-Saharan Africa. Data from successive Demographic and Health Surveys undertaken in nine African countries were analyzed. Logistic regression was used to explain changes in the proportion of short birth intervals in four countries with relatively high use of reversible contraception. The overall odds ratio for the trend was 0.90 (95% CI 0.84 to 0.95) and this was unaffected by adjusting for the other variables. The odds of a short birth interval were reduced by exclusive breastfeeding (OR 0.67, 95% CI 0.58 to 0.78) and increased by use of injectable contraception (OR 1.23, 95% CI 1.11 to 1.38). The proportion of short birth intervals has changed little over the last decade in a context of very low use of the intrauterine device. Widespread adoption of injectable contraception is associated with greater odds of a short birth interval, thus not contributing favorable conditions for improved child health.


Unresolved issues in anticoagulant therapy.
Large randomized clinical trials have clarified some issues of anticoagulation and have led to progress, such as outpatient treatment of acute deep vein thrombosis with low-molecular-weight heparin. However, many uncertainties remain and are reviewed here. When should thrombolytic therapy be used, apart from patients in shock due to pulmonary embolism? How should low-molecular-weight heparin be used in patients with extreme obesity or renal failure? The optimal duration of anticoagulation after venous thromboembolism has been the subject of many debates. With the recognition of an increasing number of risk factors for recurrence, the picture becomes increasingly complex. Lower intensity of anticoagulation with vitamin K antagonists and novel anticoagulant drugs are possible alternatives in extended secondary prophylaxis. For stroke prophylaxis in non-valvular atrial fibrillation, there is a gray zone between the groups where there is a clear indication for aspirin or for vitamin K antagonists. Anticoagulation in connection with cardioversion raises questions regarding optimal postprocedure therapy. Fine tuning of prophylaxis against thromboembolism in patients with prosthetic heart valves requires more studies of subgroups, homogenous for position and type of valve as well as presence of atrial fibrillation. The management of these patients in case of surgical procedures has not been studied properly. Secondary prophylaxis after myocardial infarction may achieve the best effect with vitamin K antagonists at an INR of 2.0-2.5 in combination with low-dose aspirin, but is it really cost-effective? Finally, many controversies exist regarding anticoagulation during pregnancy.


The Cell Adhesion Activity of the Joining Peptide of Proopiomelanocortin.
Proopiomelanocortin (POMC) is a precursor protein of several peptide hormones, such as ACTH and β-endorphin. Almost all of the peptide hormones in POMC have been drastically investigated in terms of their biological activities. However, the biological activity of the joining peptide region (JP) in POMC is unknown. Therefore, to explore the biological activity of JP, sequence analyses of mammalian POMC were performed. We found an -Arg-Gly-Asp- (RGD) motif in several mammalian species, such as porcine, suggesting that JP has cell adhesion activity. To validate this hypothesis, the cell adhesion activities of the synthetic porcine JP peptides were examined using 293T cells. Cell adhesions were observed in a concentration-dependent manner of the JP peptides. In addition, the JP peptide competitively inhibited cell adhesion to the POMC-coated plates. Moreover, the cell adhesion activity of the joining peptide was inhibited by the addition of EDTA, indicating that the JP peptide mediates the cell adhesion activity via a receptor protein, integrin. Interestingly, a human JP peptide, which possesses an -Arg-Ser-Asp- (RSD) sequence in place of the RGD sequence, exhibited a higher ability in the cell adhesion activity than that of the porcine JP peptide, suggesting that the cell adhesion activity of the joining peptide is developed during the molecular evolution of POMC. In conclusion, our results reveal that the joining peptide in POMC plays an important role during cell adhesion and provide useful information related to signal transduction of nerve peptide hormones derived from POMC.


Secular Trends in Incidence, Modality and Mortality with Dialysis Receiving AKI in Children in Ontario: A Population-Based Cohort Study.
There is a limited appreciation of the epidemiology of dialysis-receiving AKI in children. The primary objective of the study was to evaluate changes in the incidence of dialysis-receiving AKI among children over a period of 20 years in Ontario, Canada. The secondary objectives were to assess temporal trends in the utilization of various dialysis modalities and 30-day mortality among children with dialysis-receiving AKI. All children (29 days to 18 years) who received their first dialysis for AKI between 1996 and 2015 were identified from healthcare administrative databases. Those who received dialysis for ESKD, inborn errors of metabolism, and poisonings were excluded. The incidence rates of dialysis-receiving AKI were reported annually. The Cochran-Armitage test was used to assess trends in the incidence and short-term mortality after dialysis-receiving AKI. We identified 1394 children treated with dialysis for AKI during a hospital stay. There was a significant increase in the incidence of dialysis-receiving AKI among hospitalized children from 1996 (0.58 per 1000 person-years) to 2015 (0.65 per 1000 person-years) (P=0.01). The use of continuous kidney replacement therapy and intermittent hemodialysis increased whereas the relative use of peritoneal dialysis declined over time. Thirty-day mortality rates after dialysis-receiving AKI increased from 14% to 25% between 1996 and 2009 and reduced to 19% in the more recent years (P=0.03). In Ontario, the incidence of dialysis-receiving AKI among children has increased between 1996 and 2015. The use of peritoneal dialysis for AKI has declined and the short-term mortality after dialysis-receiving AKI has increased.


Point-of-care Ultrasound in Early Diagnosis of Cardiomyopathy in a Child with Viral Myocarditis: A Case Report.
Pediatric myocarditis is a commonly missed diagnosis in the pediatric emergency department (ED) with high morbidity and mortality. The presentation of cardiogenic shock secondary to myocarditis and septic shock can be difficult to differentiate during initial resuscitation, and incorrect treatment can lead to poor prognosis. Early diagnosis may provide a better prognosis for this life-threatening condition. We report a case of a five-year-old female who presented to the ED with non-specific symptoms of myocarditis. Rapid point-of-care ultrasound led to early diagnosis, correct management, and great prognosis for the patient. Providers must maintain a high index of suspicion for cardiogenic shock in patients with nonspecific symptoms and fluid unresponsiveness. Point-of-care ultrasound can help in the identification of cardiac disorders and guide practitioners in their management plans.


Evaluation of the Edgegard laminar flow hood.
In a horizontal back-to-front flow high-efficiency particulate air-filtered laminar hood, it is shown that a Blake bottle obstruction to the air flow causes a downstream cone of turbulent air which can draw microbial contamination into the work area of the hood. In controlled experiments, contamination with T3 coliphage was reduced by a series of perforations around the open edge of the hood which eliminates the cone of turbulent air. The average reduction in phage counts was 90.75, 86.79, 91.12, and 98.92%, depending upon the site of nebulization. The phage counts were reduced in 48 of the 51 tests.


Challenges for the Pro-Life Movement in a Post-Roe Era.
This article argues that state laws banning abortions for disability violate reproductive justice for parents with disabilities. These bans deprive people with disabilities of choices that may be important to their possibilities of becoming parents, including possibilities for abortion of pregnancies that have become risky to continue. Far from protecting disability civil rights, these state law bans restrict the abilities of people with disabilities to choose to have children and to parent.


Constructing molecule-metal relay catalysis over heterophase metallene for high-performance rechargeable zinc-nitrate/ethanol batteries.
Zinc-nitrate batteries can integrate energy supply, ammonia electrosynthesis, and sewage disposal into one electrochemical device. However, current zinc-nitrate batteries still severely suffer from the limited energy density and poor rechargeability. Here, we report the synthesis of tetraphenylporphyrin (tpp)-modified heterophase (amorphous/crystalline) rhodium-copper alloy metallenes (RhCu M-tpp). Using RhCu M-tpp as a bifunctional catalyst for nitrate reduction reaction (NO3RR) and ethanol oxidation reaction in neutral solution, a highly rechargeable and low-overpotential zinc-nitrate/ethanol battery is successfully constructed, which exhibits outstanding energy density of 117364.6 Wh kg-1cat, superior rate capability, excellent cycling stability of ~400 cycles, and potential ammonium acetate production. Ex/in situ experimental studies and theoretical calculations reveal that there is a molecule-metal relay catalysis in NO3RR over RhCu M-tpp that significantly facilitates the ammonia selectivity and reaction kinetics via a low energy barrier pathway. This work provides an effective design strategy of multifunctional metal-based catalysts toward the high-performance zinc-based hybrid energy systems.


Small vessel and total coronary blood volume during intracoronary adenosine.
The effect of a maximally dilating dose of intracoronary adenosine on total (CBV) and small-vessel blood volume (MSVBV, an index of open-capillary density), hematocrit (MSVHct), and related parameters of O2 supply-demand ratio was examined in left ventricular myocardium of anesthetized open-chest dogs. CBV was measured from washout of 51Cr-labeled red blood cells (RBC) and MSVBV and MSVHct from contents of 51Cr-RBC and plasma label, either 131I-serum albumin or 59Fe-siderophilin, in samples of myocardium and blood. Coronary blood flow (CBF) was measured by electromagnetic flowmeter. Myocardial oxygen consumption (MVO2) was computed with the Fick equation. Myocardial oxygen tension (MPO2) was measured with bare-tipped platinum electrodes. Adenosine raised CBV 75%, CBF, 574%, and MPO2 122%, but did not affect significantly MSVBV, MSVHct, or MVO2. These results indicate that infusion of adenosine into a coronary artery perfused at constant pressure causes relaxation of smooth muscle of arteriolar resistance vessels and of other vessels larger than 100 micrometers diam, but not that of the precapillary sphincters. This may be explained by the opposing action of increased MPO2 on the sphincters when flow increases. MSVHct was consistently much less than large-vessel Hct. This warrants combined use of red blood cell and plasma labels for accurate measurements of MSVBV.


Active and passive electrical properties of single bullfrog atrial cells.
Single cells from the bullfrog (Rana catesbeiana) atrium have been prepared by using a modification of the enzymatic dispersion procedure described by Bagby et al. (1971. Nature [Long.]. 234:351--352) and Fay and Delise (1973. Proc. Natl. Acad. Sci. U.S.A. 70:641--645). Visualization of relaxed cells via phase-contrast or Nomarski optics (magnification, 400--600) indicates that cells range between 150 and 350 micrometers in length and 4 and 7 micrometers in diameter. The mean sarcomere length in relaxed, quiescent atrial cells in 2.05 micrometer. Conventional electrophysiological measurements have been made. In normal Ringer's solution (2.5 mM K+, 2.5 mM Ca++) acceptable cells have stable resting potentials of about -88 mV, and large (125 mV) long-duration (approximately 720 ms) action potentials can be elicited. The Vm vs. log[K+]0 relation obtained from isolated cells is similar to that of the intact atrium. The depolarizing phase of the action potential of isolated atrial myocytes exhibits two pharmacologically separable components: tetrodotoxin (10(-6) g/ml) markedly suppresses the initial regenerative depolarization, whereas verapamil (3 x 10(-6) M) inhibits the secondary depolarization and reduce the plateau height. A bridge circuit was used to estimate the input resistance (220 +/- 7 M omega) and time constant 20 +/- 7 ms) of these cells. Two-microelectrode experiments have revealed small differences in the electrotonic potentials recorded simultaneously at two different sites within a single cell. The equations for a linear, short cable were used to calculate the electrical constants of relaxed, single atrial cells: lambda = 921.3 +/- 29.5 micrometers; Ri = 118.1 +/- 24.5 omega cm; Rm = 7.9 +/- 1.2 x 10(3) omega cm2; Cm = 2.2 +/- 0.3 mu Fcm-2. These results and the atrial cell morphology suggest that this preparation may be particularly suitable for voltage-clamp studies.


Spontaneous pregnancy rates in Chinese men undergoing microsurgical subinguinal varicocelectomy and possible preoperative factors affecting the outcomes.
To investigate pregnancy rates after microsurgical varicocelectomy in Chinese infertile men with clinical varicoceles and to identify preoperative factors affecting the outcomes. Retrospective data analysis. University infertility clinic. One hundred seventy-six consecutive Chinese men with infertility and clinical varicoceles who underwent varicocelectomy from January 2010 to December 2011. Semen data were available for 145 patients, and pregnancy data were available for 66. Varicocelectomy was performed on all patients. Spontaneous pregnancy rates and improvement in semen parameters after varicocelectomy. We followed 145 men (82.4%) for a median of 21 months (range 12-36 months) after varicocelectomy. For 109 patients (75.2%), both sperm concentration and forward motility improved. Overall, 45.5% (66/145) of female partners achieved spontaneous pregnancy at a mean follow-up of 11.7 ± 6.2 months. On univariate analysis, preoperative high sperm concentration (≥20 million/mL) and high sperm motility (≥25%) were positively associated with spontaneous pregnancy. On multivariate analysis, only preoperative sperm concentration was an independent predictor. Microsurgical varicocelectomy could improve semen quality and spontaneous pregnancy rates. Only preoperative sperm concentration was an independent predictor of spontaneous pregnancy. Patients with high initial sperm concentration may benefit from varicocelectomy for spontaneous pregnancy.


A Comprehensive Survey of Scene Graphs: Generation and Application.
Scene graph is a structured representation of a scene that can clearly express the objects, attributes, and relationships between objects in the scene. As computer vision technology continues to develop, people are no longer satisfied with simply detecting and recognizing objects in images; instead, people look forward to a higher level of understanding and reasoning about visual scenes. For example, given an image, we want to not only detect and recognize objects in the image, but also understand the relationship between objects (visual relationship detection), and generate a text description (image captioning) based on the image content. Alternatively, we might want the machine to tell us what the little girl in the image is doing (Visual Question Answering (VQA)), or even remove the dog from the image and find similar images (image editing and retrieval), etc. These tasks require a higher level of understanding and reasoning for image vision tasks. The scene graph is just such a powerful tool for scene understanding. Therefore, scene graphs have attracted the attention of a large number of researchers, and related research is often cross-modal, complex, and rapidly developing. However, no relatively systematic survey of scene graphs exists at present. To this end, this survey conducts a comprehensive investigation of the current scene graph research. More specifically, we first summarize the general definition of the scene graph, then conducte a comprehensive and systematic discussion on the generation method of the scene graph (SGG) and the SGG with the aid of prior knowledge. We then investigate the main applications of scene graphs and summarize the most commonly used datasets. Finally, we provide some insights into the future development of scene graphs.


Rapid synthesis of nitrogen doped carbon dots and their application as a label free sensor array for simultaneous discrimination of multiple proteins.
In this work, we develop a facile one-step strategy for rapidly (within 1 min) preparing four kinds of nitrogen doped carbon dots (N-CDs) and construct a label free sensor array for protein discrimination. The monodispersed blue emitting N-CDs, with a quantum yield (QY) of about 7.6% (calibrated with quinine sulfate as the reference), were systematically characterized by using fluorescence spectroscopy, atomic force microscopy (AFM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS) and infrared spectroscopy (IR). Based on the diverse fluorescence intensity response patterns, eight proteins with diverse isoelectric points and molecular weights could be simultaneously and effectively discriminated at nanomolar concentration by linear discrimination analysis (LDA). Proteins with different concentrations or protein mixtures can also be well identified. Furthermore, multiple proteins could still be well identified without any overlap in the presence of human urine. Moreover, serums from rectal cancer patients, Alzheimer's disease patients and healthy people could be effectively discriminated, showing great potential in auxiliary clinical diagnosis.


Offline crime bounces back to pre-COVID levels, cyber stays high: interrupted time-series analysis in Northern Ireland.
Much research has shown that the first lockdowns imposed in response to the COVID-19 pandemic were associated with changes in routine activities and, therefore, changes in crime. While several types of violent and property crime decreased immediately after the first lockdown, online crime rates increased. Nevertheless, little research has explored the relationship between multiple lockdowns and crime in the mid-term. Furthermore, few studies have analysed potentially contrasting trends in offline and online crimes using the same dataset. To fill these gaps in research, the present article employs interrupted time-series analysis to examine the effects on offline and online crime of the three lockdown orders implemented in Northern Ireland. We analyse crime data recorded by the police between April 2015 and May 2021. Results show that many types of traditional offline crime decreased after the lockdowns but that they subsequently bounced back to pre-pandemic levels. In contrast, results appear to indicate that cyber-enabled fraud and cyber-dependent crime rose alongside lockdown-induced changes in online habits and remained higher than before COVID-19. It is likely that the pandemic accelerated the long-term upward trend in online crime. We also find that lockdowns with stay-at-home orders had a clearer impact on crime than those without. Our results contribute to understanding how responses to pandemics can influence crime trends in the mid-term as well as helping identify the potential long-term effects of the pandemic on crime, which can strengthen the evidence base for policy and practice.


A Scoping Review of "Responsible Drinking" Interventions.
Public health groups, researchers, the beverage alcohol industry, and other stakeholders have promoted and applied the concept of "responsible drinking" for the past 50 years. However, little is known about the state of the existing responsible drinking evaluation research and its application to policy and practice. This project provides a scoping review of studies evaluating responsible drinking interventions. Two primary research questions guided this investigation: (1) To what extent have authors attempted to define the concept of responsible drinking while evaluating responsible drinking interventions? and (2) What is the state of the responsible drinking intervention evaluation literature? We retrieved 49 peer-reviewed articles that evaluated interventions designed to promote "responsible drinking." Four articles provided, or attempted to provide, an explicit definition of responsible drinking; these four definitions lacked consensus. The existing responsible drinking interventions varied considerably in terms of the messages they attempted to convey (e.g., avoid binge drinking, use protective behavioral strategies, stick to relatively safe drinking limits), again suggesting lack of consensus. We observed greater consensus concerning the approach to evaluating responsible drinking interventions: studies typically recruited college students to complete brief, well-controlled experiments and measured potential predictors of drinking behavior (e.g., attitudes, expectancies, intentions) rather than actual drinking behavior. We discuss limitations of this methodological approach and the need for greater consensus regarding the concept of responsible drinking.


Racial distribution of Dupuytren's disease in Department of Veterans Affairs patients.
Dupuytren's disease is a polyclonal fibroproliferative disorder of the palmar fascia of unclear pathogenesis. It has been described as a disease of northern European men and is reportedly rare in other races. A 10-year retrospective study using the Department of Veterans Affairs computer system was conducted to determine the racial distribution of this disorder among patients treated at all Department of Veterans Affairs medical centers. The study also determined demographic and clinical characteristics of black veterans treated for the condition at department medical centers. There were 9938 patients identified between the fiscal years of 1986 and 1995, of whom 412 were black (estimated prevalence of 130 per 100,000 population), 9071 were white (734 per 100,000), 234 were Hispanic white (237 per 100,000), 11 were Native American (144 per 100,000), 8 were Asian (67 per 100,000), and 202 were of unknown race. The characteristics of the disease in blacks are similar to those in whites. In both groups, the disease has a late onset, affects predominantly the ulnar digits, and is associated with other medical conditions, such as alcoholism, smoking, and diabetes. Unlike Dupuytren's disease in whites, however, the disease is rarely bilateral in blacks. The differential prevalence among racial groups suggests a genetic component to the pathogenesis of the disease.


Disordered eating and emotion dysregulation among adolescents and their parents.
Research on the relationships between adolescent and parental disordered eating (DE) and emotion dysregulation is scarce. Thus, the aim of this study was to explore whether mothers' and fathers' own DE, as measured by SCOFF questionnaire, and emotion dysregulation, as measured by the difficulties in emotion regulation scale (DERS), were associated with their daughters' or sons' DE and emotion dysregulation. Furthermore, the importance of shared family meals and possible parent-related predictors of adolescent DE were explored. The total sample comprised 1,265 adolescents (M age = 16.19, SD = 1.21; age range 13.5-19 years, 54.5% female) whose parents had received a self-report questionnaire via mail. Of these, 235 adolescents (18.6% of the total sample) whose parents completed the questionnaire were used in the analyses. Parents' responses were matched and compared with those of their child. Adolescent girls showed greater levels of DE overall than did their parents. Furthermore, DE was associated with emotion dysregulation among both adolescents and parents. Adolescent and parental emotion dysregulation was associated, although there were gender differences in the specifics of this relationship. The frequency of shared dinner meals was the only variable that was associated to DE and emotion dysregulation among adolescents, while parental eating disorder was the only variable that enhanced the probability of adolescent DE. The present study contributes to the literature by demonstrating that there are significant associations between parents and their adolescent children in terms of DE, emotion dysregulation, and shared family meals. Future studies should break down these relationships among mothers, fathers, girls, and boys to further clarify the specific associational, and possibly predictive, directions.


Can thromboembolic risk be associated with erectile dysfunction in atrial fibrillation patients?
Erectile dysfunction (ED) is highly prevalent in patients with diseases of cardiovascular system, including patients with atrial fibrillation (AF). Reasons for this high co-prevalence include endothelial dysfunction, inflammation, oxidative and emotional stress associated with AF. Association of AF-induced prothrombotic state and possible microthrombi in penile arteries with ED remains unclear. The present study aims to assess if probability of AF-associated risk of peripheral thromboembolism may be associated with ED in AF patients. Probability of thromboembolic complications was assessed with two commonly used risk scores CHADS₂ and CHA2DS₂-VASc in a group of continuous AF patients. All patients were also asked to fill an IIEF-5 questionnaire designed for screening for ED. Mean CHADS₂ score in the whole study group was 1.1 ± 1.0 points and CHA₂DS₂- -VASc was 1.5 ± 1.4 points. ED was present in 57.4% of the 129-person study population. In patients with ED, both CHADS₂ (0.9 ± 1.0 vs. 1.3 ± 1.1; p = 0.03) and CHA₂DS₂-VASc (1.2 ± 1.1 vs. 1.8 ± 1.5; p = 0.03) scores were significantly higher than in the group without dysfunction. After dividing the patients according to age into groups younger than 65 years vs. ≥ 65 years, observed correlation was no longer significant in the younger group (p > 0.05). In patients ≥ 65 years, in whom the risk scores are routinely used, dysfunction both CHADS₂ (1.1 ± 0.9 vs. 2.0 ± 0.9; p = 0.02) and CHA₂DS₂-VASc (2.3 ± 1.1 vs. 3.4 ± 1.3; p = 0.04) scores were higher in the group with ED. Erectile dysfunctions in AF patients are associated with elevated cardioembolic risk. We postulate that the diagnosis of ED should be considered an additional marker of prothrombotic state, and may be useful in clinical decision-making, especially in patients ≥ 65 years old.


The Role of Dynamic miRISC During Neuronal Development.
Activity-dependent protein synthesis plays an important role during neuronal development by fine-tuning the formation and function of neuronal circuits. Recent studies have shown that miRNAs are integral to this regulation because of their ability to control protein synthesis in a rapid, specific and potentially reversible manner. miRNA mediated regulation is a multistep process that involves inhibition of translation before degradation of targeted mRNA, which provides the possibility to store and reverse the inhibition at multiple stages. This flexibility is primarily thought to be derived from the composition of miRNA induced silencing complex (miRISC). AGO2 is likely the only obligatory component of miRISC, while multiple RBPs are shown to be associated with this core miRISC to form diverse miRISC complexes. The formation of these heterogeneous miRISC complexes is intricately regulated by various extracellular signals and cell-specific contexts. In this review, we discuss the composition of miRISC and its functions during neuronal development. Neurodevelopment is guided by both internal programs and external cues. Neuronal activity and external signals play an important role in the formation and refining of the neuronal network. miRISC composition and diversity have a critical role at distinct stages of neurodevelopment. Even though there is a good amount of literature available on the role of miRNAs mediated regulation of neuronal development, surprisingly the role of miRISC composition and its functional dynamics in neuronal development is not much discussed. In this article, we review the available literature on the heterogeneity of the neuronal miRISC composition and how this may influence translation regulation in the context of neuronal development.


An epizootic of respiratory syncytial virus infection in a dairy herd.
Respiratory syncytial virus was the cause of a severe epizootic of bovine respiratory tract disease. The virus, isolated from a sick cow during the epizootic, produced cytopathic effect in a bovine turbinate cell line 14 days after it was inoculated. Additional support for the diagnosis came from the results of pathologic and serologic examinations. Lesions consistently present were severe necrotizing bronchiolitis and epithelial syncytia projecting from bronchiolar and alveolar walls. Also, in the cow from which the virus was isolated, there was tracheitis with a syncytial-like change involving the mucosal epithelium.


A study of the YopD-lcrH interaction from Yersinia pseudotuberculosis reveals a role for hydrophobic residues within the amphipathic domain of YopD.
The enteropathogen Yersinia pseudotuberculosis is a model system used to study the molecular mechanisms by which Gram-negative pathogens translocate effector proteins into target eukaryotic cells by a common type III secretion machine. Of the numerous proteins produced by Y. pseudotuberculosis that act in concert to establish an infection, YopD (Yersinia outer protein D) is a crucial component essential for yop regulation and Yop effector translocation. In this study, we describe the mechanisms by which YopD functions to control these processes. With the aid of the yeast two-hybrid system, we investigated the interaction between YopD and the cognate chaperone LcrH. We confirmed that non-secreted LcrH is necessary for YopD stabilization before secretion, presumably by forming a complex with YopD in the bacterial cytoplasm. At least in yeast, this complex depends upon the N-terminal domain and a C-terminal amphipathic alpha-helical domain of YopD. Introduction of amino acid substitutions within the hydrophobic side of the amphipathic alpha-helix abolished the YopD-LcrH interaction, indicating that hydrophobic, as opposed to electrostatic, forces of attraction are important for this process. Suppressor mutations isolated within LcrH could compensate for defects in the amphipathic domain of YopD to restore binding. Isolation of LcrH mutants unable to interact with wild-type YopD revealed no single domain responsible for YopD binding. The YopD and LcrH mutants generated in this study will be relevant tools for understanding YopD function during a Yersinia infection.


Therapeutic use of colony stimulating factors for established neutropenic fever.
The hematopoietic growth factors granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are approved only for prophylaxis of infectious complications secondary to the use of chemotherapy, yet both are often used off-label therapeutically in conjunction with antibiotics following the onset of neutropenic fever. Several recent trials have evaluated the use of CSFs as adjuncts to antibiotic therapy for the management of patients presenting with neutropenic fever following chemotherapy administration. Statistically significant reductions in days of neutropenia by one or two days were observed in some trials but the clinical significance of these results is uncertain. Most trials demonstrated no reductions in duration of hospitalization, number of days of fever, or mortality. Given the current lack of data supporting the use of CSFs as adjuncts to antibiotic therapy in patients presenting with neutropenic fever, and given the high cost of these drugs, their use for this indication is not recommended at this time.


Three-dimensional microscale modelling of CO2 transport and light propagation in tomato leaves enlightens photosynthesis.
We present a combined three-dimensional (3-D) model of light propagation, CO2 diffusion and photosynthesis in tomato (Solanum lycopersicum L.) leaves. The model incorporates a geometrical representation of the actual leaf microstructure that we obtained with synchrotron radiation X-ray laminography, and was evaluated using measurements of gas exchange and leaf optical properties. The combination of the 3-D microstructure of leaf tissue and chloroplast movement induced by changes in light intensity affects the simulated CO2 transport within the leaf. The model predicts extensive reassimilation of CO2 produced by respiration and photorespiration. Simulations also suggest that carbonic anhydrase could enhance photosynthesis at low CO2 levels but had little impact on photosynthesis at high CO2 levels. The model confirms that scaling of photosynthetic capacity with absorbed light would improve efficiency of CO2 fixation in the leaf, especially at low light intensity.


Laboratory testing for factor inhibitors.
Inhibitor assays are performed when patients present with unexplained prolonged routine coagulation test times and unexpected and/or unusual bleeding (potential for acquired haemophilia) as well as being a part of normal congenital haemophilia management and monitoring, particularly when bleeding occurs on therapy, or when increments in factor levels post-factor replacement remain lower than expected. In this article, we will describe the assays used, as well as their development, pitfalls in testing such as inter-laboratory variability and false negative/positive results, as well as some strategies for overcoming these pitfalls and potential alternative test approaches. The inter-laboratory coefficient of variation often approaches (and sometimes exceeds) 50%, as evidenced by various external quality assessment groups, and this variability has not improved over recent years. Additional important considerations include appropriate interpretation of test results, repeat testing for confirmation, and assessment of recovery as part of the diagnostic process.


Reconfigurable all-diffractive optical filters using phase-only spatial light modulators.
We demonstrate a reconfigurable optical filter implemented using a phase-only two-dimensional liquid-crystal-on-silicon spatial light modulator. To achieve this we utilize two different approaches leading to two different configurations in the modulator. The first one, based on a spatially patterned diffractive lens, permits us to obtain the desired spectrum along the optical axis and, in the second one, which is based on a generalized spectrometer, the desired spectrum is found outside of the optical axis. Experimental results show good agreement with the theory and indicate the validity of this technique.


Bim polymorphisms: influence on function and response to treatment in children with acute lymphoblastic leukemia.
Corticosteroids induce apoptosis in the malignant lymphoid cells and are critical component of combination therapy for acute lymphoblastic leukemia (ALL). Several genome-wide microarray studies showed major implication of proapoptotic Bim in mediating corticosteroid-related resistance in leukemia cells. We investigated Bim gene polymorphisms and their association with childhood ALL outcome, and the mechanism underlying the observed finding. Lower overall survival (OS) was associated with Bim C29201T located in Bcl-2 homology 3 (BH3) domain (P = 0.01). An association remained significant in multivariate model (P = 0.007), was more apparent in high-risk patients (P = 0.004) and patients treated with dexamethasone (P = 0.009), and was subsequently confirmed in the replication patient cohort (P = 0.03). RNA analysis revealed that C29201T affects generation of γ isoforms (γ1) that lack proapoptotic BH3 domain. The phenotypic effect was minor suggesting the influence of additional factors that may act in conjunction with Bim genotype. Combined analysis with Mcl gene polymorphism (G-486T) revealed profound reduction in OS in individuals with both risk genotypes (P < 0.0005 in discovery and P = 0.002 in replication cohort) and particularly in high-risk patients (P ≤ 0.008). Increased expression of prosurvival Mcl1 and presence of Bim isoforms lacking proapoptotic function might explain marked reduction of OS in a disease and dose-dependent manner in ALL patients carrying Bim- and Mcl1-risk genotypes.


Racial differences in seroprevalence of HAV and HEV in blood donors in the Western Cape, South Africa: a clue to the predominant HEV genotype?
Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. This infection causes major water-borne outbreaks in low- and middle-income countries, whilst in industrialised countries this infection is zoonotic. These differences in epidemiology are related to different HEV genotypes. HEV genotype 3 is a zoonotic infection, whilst genotype 2 causes large outbreaks. This study determined the seroprevalence of HEV in blood donors from the Western Cape. Anti-hepatitis A virus (anti-HAV) antibody was detected in 184/300 (61%) donors. Antibody to HEV (anti-HEV) was detected in 78 of 300 donors (26%). It was highest in mixed race donors (62/100), followed by white donors (23/100) and lowest in black donors (19/100) P = 0.019. Since it is thought that genotypes 1 and 2 predominate both viruses would be acquired by the oro-faecal route, it is surprising that HEV seroprevalence does not mirror that of HAV. We postulate that this may reflect differences in socio-economic status and consumption of dietary meat. So the marked divergence between HEV and HAV seroprevalence may be the result of different routes of transmission. Further data are needed to explore the risk factors associated with HEV infection.


Exploring and visualizing multidimensional data in translational research platforms.
The unprecedented advances in technology and scientific research over the past few years have provided the scientific community with new and more complex forms of data. Large data sets collected from single groups or cross-institution consortiums containing hundreds of omic and clinical variables corresponding to thousands of patients are becoming increasingly commonplace in the research setting. Before any core analyses are performed, visualization often plays a key role in the initial phases of research, especially for projects where no initial hypotheses are dominant. Proper visualization of data at a high level facilitates researcher's abilities to find trends, identify outliers and perform quality checks. In addition, research has uncovered the important role of visualization in data analysis and its implied benefits facilitating our understanding of disease and ultimately improving patient care. In this work, we present a review of the current landscape of existing tools designed to facilitate the visualization of multidimensional data in translational research platforms. Specifically, we reviewed the biomedical literature for translational platforms allowing the visualization and exploration of clinical and omics data, and identified 11 platforms: cBioPortal, interactive genomics patient stratification explorer, Igloo-Plot, The Georgetown Database of Cancer Plus, tranSMART, an unnamed data-cube-based model supporting heterogeneous data, Papilio, Caleydo Domino, Qlucore Omics, Oracle Health Sciences Translational Research Center and OmicsOffice® powered by TIBCO Spotfire. In a health sector continuously witnessing an increase in data from multifarious sources, visualization tools used to better grasp these data will grow in their importance, and we believe our work will be useful in guiding investigators in similar situations.


Mitral Inflow Obstruction Resulting From a Dilated Coronary Sinus: Role of Intraoperative Transesophageal Echocardiography in Diagnosis and Surgical Repair: A Case Report.
Mitral inflow obstruction caused by dilated coronary sinus is a rare congenital cardiac anomaly that must be differentiated from other causes of left ventricular inflow obstruction such as cor triatriatum, supramitral membrane, and supramitral ridge, because their surgical repair is different. Although preoperative transthoracic echocardiography is the primary imaging modality for diagnosis, intraoperative transesophageal echocardiography has a higher sensitivity and specificity over transthoracic echocardiography in differentiating these lesions. We report 2 cases of supramitral obstruction where the intraoperative transesophageal echocardiography has refined the preoperative diagnosis and changed the course of surgical repair.


Use of routinely captured echocardiographic data in the diagnosis of severe aortic stenosis.
To determine the implications of applying guideline-recommended definitions of aortic stenosis to echocardiographic data captured in routine clinical care. Retrospective observational study of 213 174 patients who underwent transthoracic echocardiographic imaging within Allina Health between January 2013 and October 2017. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of echocardiographic measures for severe aortic stenosis were determined relative to the documented interpretation of severe aortic stenosis. Among 77 067 patients with complete assessment of the aortic valve, 1219 (1.6%) patients were categorised as having severe aortic stenosis by the echocardiographic reader. Relative to the documented interpretation, aortic valve area (AVA) as a measure of severe aortic stenosis had the high sensitivity (94.1%) but a low positive predictive value (37.5%). Aortic valve peak velocity and mean gradient were specific (>99%), but less sensitive (<70%). A measure incorporating peak velocity, mean gradient and dimensionless index (either by velocity time integral or peak velocity ratio) achieved a balance of sensitivity (92%) and specificity (99%) with little detriment in accuracy relative to peak velocity and mean gradient alone (98.9% vs 99.3%). Using all available data, the proportion of patients whose echocardiogram could be assessed for aortic stenosis was 79.8% as compared with 52.7% by documented interpretation alone. A measure that used dimensionless index in place of AVA addressed discrepancies between quantitative echocardiographic data and the documented interpretation of severe aortic stenosis. These findings highlight the importance of understanding the limitations of clinical data as it relates to quality improvement efforts and pragmatic research design.


Infectious mononucleosis patients temporarily recognize a unique, cross-reactive epitope of Epstein-Barr virus nuclear antigen-1.
The spectrum of antibodies against Epstein-Barr virus nuclear antigen-1 (EBNA-1) in patients with a recent history of infectious mononucleosis and nonaffected EBV-positive individuals has been characterized by epitope mapping. Sera were evaluated for antibodies to all unique maximally overlapping octapeptides of EBNA-1. Both normal controls and patients with infectious mononucleosis produce IgG antibodies that recognize the glycine-alanine-rich portion of EBNA-1, as previously described. All EBNA-1 IgG-positive infectious mononucleosis patients tested, however, consistently produce IgG specific for an additional epitope (aa 398-412 PPPGRRPFFHPVGEA) near the middle of the EBNA-1 protein. This region was not found to be antigenic in healthy EBV-seropositive individuals. This region does, however, cross-react with the sequence PPPGMRPP from the common lupus spliceosomal autoantigen Sm B' in several infectious mononucleosis patient sera. Patients with recent clinical infectious mononucleosis temporarily recognize a unique cross-reactive epitope of EBNA-1 not bound by antibodies from non-infectious mononucleosis EBV-positive sera or those with a distant history of IM.


Synthesis of 5-Aminolevulinic Acid-Based ALACELL Possessing Inhibitory Effect against Cutibacterium acnes: Whitening Effect and Protective Effect of UVB-Irradiated Damage Cells.
Five-aminolevulinic acid (5-ALA)-photodynamic therapy combined with infrared radiation is an effective and safe therapy for facial acne. Although there are various available agents for treating acne, therapies for resistant or severe strains have been limited. The aim of this study was to investigate the inhibitory efficacy of ALACELL synthesized by combining 5-ALA with Y-G-G-F-L peptide against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Yersinia enterocolitica, as well as Cutibacterium acnes. Furthermore, other effects of ALACELL on human skin cells, melanin formation, intracellular tyrosinase activity, and Ultra Violet B (UVB)-irradiated cell death were measured by treatment of ALACELL in vitro. ALACELL particularly showed a growth inhibitory effect on C. acnes and no inhibitory effect on the four bacteria strains. ALACELL reduced melanin formation and intracellular tyrosinase activity by α-melanin cell-stimulating hormone (α-MSH) in B16F10 cells, with no cytotoxicity. ALACELL also improved cell viability in UVB-irradiated HaCaT cells. The results of the experiment show that ALACELL exhibits more efficacy than 5-ALA against antimicrobial activity, melanin formation, intracellular tyrosinase activity, and UVB-irradiated cell death. Therefore, ALACELL is recommended as a candidate for clinical application in the treatment of acne and skin aging and will be further investigated to study the mode of action and in actual situations.


Computational modeling of the negative priming effect based on inhibition patterns and working memory.
Negative priming (NP), slowing down of the response for target stimuli that have been previously exposed, but ignored, has been reported in multiple psychological paradigms including the Stroop task. Although NP likely results from the interplay of selective attention, episodic memory retrieval, working memory, and inhibition mechanisms, a comprehensive theoretical account of NP is currently unavailable. This lacuna may result from the complexity of stimuli combinations in NP. Thus, we aimed to investigate the presence of different degrees of the NP effect according to prime-probe combinations within a classic Stroop task. We recorded reaction times (RTs) from 66 healthy participants during Stroop task performance and examined three different NP subtypes, defined according to the type of the Stroop probe in prime-probe pairs. Our findings show significant RT differences among NP subtypes that are putatively due to the presence of differential disinhibition, i.e., release from inhibition. Among the several potential origins for differential subtypes of NP, we investigated the involvement of selective attention and/or working memory using a parallel distributed processing (PDP) model (employing selective attention only) and a modified PDP model with working memory (PDP-WM, employing both selective attention and working memory). Our findings demonstrate that, unlike the conventional PDP model, the PDP-WM successfully simulates different levels of NP effects that closely follow the behavioral data. This outcome suggests that working memory engages in the re-accumulation of the evidence for target response and induces differential NP effects. Our computational model complements earlier efforts and may pave the road to further insights into an integrated theoretical account of complex NP effects.


FiberWire is superior in strength to stainless steel wire for tension band fixation of transverse patellar fractures.
The metal implants used to achieve fixation of displaced transverse patellar fractures are associated with implant failure, postoperative pain and a significant re-operation rate. Recent studies have examined braided suture as a possible alternative to stainless steel wire to increase patient satisfaction and decrease re-operation rates, but suture has not demonstrated clearly superior fixation strength. FiberWire is a reinforced braided polyblend suture that has demonstrated superior characteristics to the previous sutures studied and has not to our knowledge been examined as a material for tension band fixation of transverse patellar fractures. Materials testing was performed on repeated samples of No. 5 FiberWire suture and 18-gauge stainless steel wire. The strength and stiffness of each material was measured. The two materials were then used for tension band fixation on a novel transverse patellar fracture model and tested to failure by three-point bending. The constructs included a single stainless steel wire, a single-strand FiberWire tied with a sliding knot, double-strand FiberWire tied with sliding knots and double-strand FiberWire tied with a Wagoner's Hitch. The fixation strength and stiffness of the constructs were measured. Unlike stainless steel, FiberWire maintained its initial stiffness until failure. Furthermore, during three-point-bend testing, double-strand FiberWire was found to have a significantly higher failure load than stainless steel wire when the suture was tied and locked under the tension produced by a modified Wagoner's Hitch. FiberWire is a potentially superior alternative to stainless steel wire in tension band fixation of transverse patellar fractures.


Remodeling of Rectal Innervation After Pullthrough Surgery for Hirschsprung Disease: Relevance to Criteria for the Determination of Retained Transition Zone.
After pullthrough surgery for Hirschsprung disease (HSCR), Glut1-positive submucosal nerve hypertrophy is used to diagnose retained transition zone in the neorectum. We hypothesized that pelvic nerves, severed during pullthrough surgery, sprout into the neorectum to mimic transition zone. The density (nerves/100x field) and maximum diameter of Glut1-positive submucosal nerves were measured in biopsies and redo resections from 20 patients with post-pullthrough obstructive symptoms. Their original and/or redo resections excluded unequivocal features of transition zone (myenteric hypoganglionosis or partial circumferential aganglionosis) in 17. Postoperative values were compared with control data from 28 cadaveric and 6 surgical non-HSCR specimens, and 14 primary HSCR resections. When possible, nerves were tracked from attached native pelvic soft tissue or aganglionic rectal cuff into the pulled-through colon. Glut1-positive submucosal nerves were not present in the 11 colons of non-HSCR infants less than 1 year of age, except sparsely in the rectum. In 17 older non-HSCR controls, occasional Glut1-positive nerves were observed in prerectal colon and were larger and more numerous in the rectum. In redo resections, Glut1-positive submucosal innervation in post-pullthrough specimens did not differ significantly from age-appropriate non-HSCR rectal controls and pelvic Glut1-positive nerves were never observed to penetrate the pulled-through colon. However, the density and caliber of Glut1-positive nerves in the neorectums were significantly greater than expected based on the prerectal location from which the pulled-through bowel originated. Submucosal innervation in post-pullthrough specimens does not support the hypothesis that native pelvic nerves innervate the neorectum, but suggests remodeling occurs to establish the age-appropriate density and caliber of rectal Glut1-positive innervation. The latter should not be interpreted as transition zone pullthrough in a rectal biopsy from a previously done pullthrough.


COVID-19 Pandemic: Experiences in China and Implications for its Prevention and Treatment Worldwide.
The outbreak of COVID-19 due to SARS-CoV-2 originally emerged in Wuhan in December 2019. As of March 22, 2020, the disease spread to 186 countries, with at least 305,275 confirmed cases. Although there has been a decline in the spread of the disease in China, the prevalence of COVID-19 around the world remains serious despite containment efforts undertaken by national authorities and the international community. In this article, we systematically review the brief history of COVID-19 and its epidemic and clinical characteristics, highlighting the strategies used to control and prevent the disease in China, which may help other countries respond to the outbreak. This pandemic emphasizes the need to be constantly alert to shifts in both the global dynamics and the contexts of individual countries, making sure that all are aware of which approaches are successful for the prevention, containment and treatment of new diseases, and being flexible enough to adapt the responses accordingly.


An essential role of ubiquitination in Cbl-mediated negative regulation of the Src-family kinase Fyn.
The Cbl family of ubiquitin ligases function as negative regulators of activated receptor tyrosine kinases by facilitating their ubiquitination and subsequent lysosomal targeting. Here, we have investigated the role of Cbl ubiquitin ligase activity in the negative regulation of a non-receptor tyrosine kinase, the Src-family kinase Fyn. Using primary embryonic fibroblasts from Cbl(+/+) and Cbl(-/-) mice, we demonstrate that endogenous Cbl mediates the ubiquitination of Fyn and dictates the rate of Fyn turnover. By analyzing CHO-TS20 cells with a temperature-sensitive ubiquitin activating enzyme, we demonstrate that intact cellular ubiquitin machinery is required for Cbl-induced degradation of Fyn. Analyses of Cbl mutants, with mutations in or near the RING finger domain, in 293T cells revealed that the ubiquitin ligase activity of Cbl is essential for Cbl-induced degradation of Fyn by the proteasome pathway. Finally, use of a SRE-luciferase reporter demonstrated that Cbl-dependent negative regulation of Fyn function requires the region of Cbl that mediates the ubiquitin ligase activity. Given the conservation of structure between various Src-family kinases and the ability of Cbl to interact with multiple members of this family, Cbl-dependent ubiquitination could serve a general role to negatively regulate activated Src-family kinases.


Performance physique et densité minérale osseuse chez de jeunes adultes libanais.
The aim of this study was to explore the relationships between performances obtained in different physical tests and bone parameters (bone mineral density (BMD) and bone mineral content (BMC)) in a group of young Lebanese adults. One hundred and six young Lebanese adults (45 women and 61 men) whose ages range from 17 to 34 years participated in this study. Weight and height were measured, and body mass index (BMI) was calculated. Daily calcium intake, daily protein intake and physical activity level (h/week) were evaluated using validated questionnaires. The level of physical performance was measured using several physical tests: vertical-jump test, standing long jump test, 3-jumptest, 5-jump-test and 1-RM half-squat. Body composition, bone mineral content (BMC) and BMD at whole body (WB), lumbar spine (L2-L4), total hip (TH) and femoral neck (FN) were measured by dual-energy X-ray absorptiometry (DXA). In women, height, lean mass, 1- RM half-squat and performances obtained in three physical tests (vertical jump test, 5-jump-test and 1-RM halfsquat) were positively correlated to BMD and BMC. In men, lean mass and 1-RM half-squat were positively correlated to BMD and BMC. This study suggests that lean mass and maximum strength obtained in half-squat are positively correlated to BMD in young adults.


Functionally critical residues in the aminoglycoside resistance-associated methyltransferase RmtC play distinct roles in 30S substrate recognition.
Methylation of the small ribosome subunit rRNA in the ribosomal decoding center results in exceptionally high-level aminoglycoside resistance in bacteria. Enzymes that methylate 16S rRNA on N7 of nucleotide G1405 (m7G1405) have been identified in both aminoglycoside-producing and clinically drug-resistant pathogenic bacteria. Using a fluorescence polarization 30S-binding assay and a new crystal structure of the methyltransferase RmtC at 3.14 Å resolution, here we report a structure-guided functional study of 30S substrate recognition by the aminoglycoside resistance-associated 16S rRNA (m7G1405) methyltransferases. We found that the binding site for these enzymes in the 30S subunit directly overlaps with that of a second family of aminoglycoside resistance-associated 16S rRNA (m1A1408) methyltransferases, suggesting that both groups of enzymes may exploit the same conserved rRNA tertiary surface for docking to the 30S. Within RmtC, we defined an N-terminal domain surface, comprising basic residues from both the N1 and N2 subdomains, that directly contributes to 30S-binding affinity. In contrast, additional residues lining a contiguous adjacent surface on the C-terminal domain were critical for 16S rRNA modification but did not directly contribute to the binding affinity. The results from our experiments define the critical features of m7G1405 methyltransferase-substrate recognition and distinguish at least two distinct, functionally critical contributions of the tested enzyme residues: 30S-binding affinity and stabilizing a binding-induced 16S rRNA conformation necessary for G1405 modification. Our study sets the scene for future high-resolution structural studies of the 30S-methyltransferase complex and for potential exploitation of unique aspects of substrate recognition in future therapeutic strategies.


Solution-Focused Coaching in Pediatric Rehabilitation: Perceived Therapist Impact.
Aims: This qualitative descriptive study explored perceived impacts of solution-focused coaching in pediatric rehabilitation (SFC-peds) from the viewpoint of experienced therapists.Methods: Semi-structured in-depth interviews were conducted with six participants (four occupational therapists and two physical therapists) who had incorporated SFC-peds into their practice for three years or longer. Participants were asked to describe perceived differences SFC-peds has made to their clinical practice, service provision, and relationships with clients and families. Interview transcripts were analyzed using the method of thematic analysis.Results: Three major themes, each with subthemes, were identified: 1) changes in therapists' perception of their roles; 2) increased service effectiveness; and 3) enhanced client capacity. Through long-term engagement with SFC-peds, participants have experienced a role shift from an expert adviser to a collaborative facilitator who assists clients and families with capacity building and self-discovery of solutions for their everyday environments.Conclusions: The findings suggest that SFC-peds can help participants reframe professional expertise and integrate principles of family-centred care into their day-to-day practice. Individual- and system-level support, along with flexibility in service structures and processes, may be needed to further the implementation of SFC-peds in service delivery.