Imprinting in neurons.
Although most imprinted genes display parent-origin-specific gene expression in tissues where they are transcribed, some genes are imprinted in a tissue-specific manner. Genes that show brain-specific imprinting or brain-specific lack of imprinting present a unique opportunity to study the process of imprinting during tissue differentiation. In this review, I introduce the systematic study of brain-cell-lineage-specific imprinting using a primary brain cell culture system, where neurons or glial cells are cultured separately. Two reports using the primary brain cell culture revealed brain-cell-lineage-specific imprinting in Ube3a and Igf2r, which had previously been described to show brain-specific imprinting and brain-specific lack of imprinting, respectively. Such brain-cell-lineage-specific imprinting was associated with cell-specific epigenetic modifications, especially with their reciprocally imprinted antisense non-coding RNAs, Ube3a-ATS and Air. These results emphasize the necessity of imprinting analysis at the cell level rather than in whole brain tissue during brain differentiation. The brain cell culture system provides us with a new powerful tool to understand the molecular mechanism of brain-specific imprinting.


Memory impairment in abstinent MDMA ("Ecstasy") users.
Methylenedioxymethamphetamine (MDMA, or "Ecstasy") is a popular recreational drug of abuse that is known to damage brain serotonergic neurons in animals and possibly humans. Few functional consequences of MDMA-induced serotonin (5-HT) neurotoxicity have been identified, either in animals or humans. This study sought to determine whether individuals with a history of extensive MDMA use showed evidence of memory impairment, because brain serotonin has been implicated in mnemonic function. The authors compared 24 abstinent MDMA users and 24 control subjects on several standardized tests of memory, after matching subjects for age, gender, educational level, and vocabulary score (a surrogate of verbal intelligence). The authors also explored correlations between changes in memory function and decrements in CSF 5-hydroxyindoleacetic acid (5-HIAA), which serves as a marker of central 5-HT neural function. Greater use of MDMA (total milligrams per month) was associated with greater impairment in immediate verbal memory (p < 0.02) and delayed visual memory (p < 0.06). Furthermore, lower vocabulary scores were associated with stronger dose-related effects, with men having greater dose-related deficits than women. Lastly, lower concentrations of CSF 5-HIAA were associated with poorer memory performance. Abstinent MDMA users have impairment in verbal and visual memory. The extent of memory impairment correlates with the degree of MDMA exposure and the reduction in brain 5-HT, as indexed by CSF 5-HIAA.


Validation of an active shape model-based semi-automated segmentation algorithm for the analysis of thigh muscle and adipose tissue cross-sectional areas.
To validate a semi-automated method for thigh muscle and adipose tissue cross-sectional area (CSA) segmentation from MRI. An active shape model (ASM) was trained using 113 MRI CSAs from the Osteoarthritis Initiative (OAI) and combined with an active contour model and thresholding-based post-processing steps. This method was applied to 20 other MRIs from the OAI and to baseline and follow-up MRIs from a 12-week lower-limb strengthening or endurance training intervention (n = 35 females). The agreement of semi-automated vs. previous manual segmentation was assessed using the Dice similarity coefficient and Bland-Altman analyses. Longitudinal changes observed in the training intervention were compared between semi-automated and manual segmentations. High agreement was observed between manual and semi-automated segmentations for subcutaneous fat, quadriceps and hamstring CSAs. With strength training, both the semi-automated and manual segmentation method detected a significant reduction in adipose tissue CSA and a significant gain in quadriceps, hamstring and adductor CSAs. With endurance training, a significant reduction in adipose tissue CSAs was observed with both methods. The semi-automated approach showed high agreement with manual segmentation of thigh muscle and adipose tissue CSAs and showed longitudinal training effects similar to that observed using manual segmentation.


Validation of the Hygicult E dipslides method in surface hygiene control: a Nordic collaborative study.
A collaborative study with Enterobacteriaceae was conducted to validate Hygicult E dipslides by comparison with violet red bile glucose agar (VRBGA) contact plates and swabbing, using stainless steel surfaces artificially contaminated with microbes at various levels. Twelve laboratories participated in the validation procedure. The total number of collaborative samples was 108. The microbial level in each sample was assessed in triplicate by using the 3 above-mentioned methods. No Enterobacteriaceae were used at the low inoculation level. At the middle inoculation level, the percentages detached from the test surfaces were 16.6 with the Hygicult E method, 15.3 with the contact plate method, and 14.6 with swabbing; at the high innoculation level, the percentages were 14.5, 15.8, and 9.8, respectively. The percentage of acceptable results after the removal of outliers was 97.2. Repeatability relative standard deviations ranged from 33.4 to 44.9%; reproducibility relative standard deviations ranged from 45.2 to 77.1%. The Hygicult E dipslide, VRBGA contact plate, and swabbing methods gave similar results at all 3 microbial levels tested: <1.0 colony-forming units (CFU)/cm2 at the low level, 1.2-1.3 CFU/cm2 at the middle level (theoretical yield 8.0 CFU/cm2), and 1.2-2.0 CFU/cm2 at the high level (theoretical yield 12.5 CFU/cm2).


[Urodynamic findings in women following operations for stress incontinence. IV. Communication: risk of recurrent incontinence (author's transl)].
Anamnestic findings and urodynamic parameters of 377 patients suffering from urinary stress incontinence were evaluated before and one year after several incontinence operations (anterior colporrhaphy, colposuspension according to a modified Marshall-Marchetti-Krantz procedure and vesico-urethral suspension according to Pereyra). Two groups were formed: group I including 246 women who experienced successful operation and group II consisting of 131 patients suffering from recurrent stress incontinence. Mean age, -parity and -body-weight did not influence the result of surgical treatment. However, there was a statistical significant difference between both groups concerning the functional urethral length (alpha U-test = 0.00118) and the maximum urethral closure pressure (alpha much less than 0.001). By the addition of the preoperatively measured functional urethral length and the maximum urethral closure pressure a new parameter was determined by which group I and group II could be separated clearly. The difference was statistical significant (alpha much less than 0.001). According to these data the risk of recurrence could be evaluated preoperatively: the cure rate below the 25th percentile (0-56) of this new parameter was 49%, in between the 25th and the 50th percentile (57-70) the cure rate was 60%, in between the 50th and 75th percentile (71-84) 75% and above the 75th percentile (x greater than 84) 79%. Our data show clearly that the addition of the function urethral length and the maximum urethral closure pressure is an useful parameter to calculate the risk of recurrence of stress incontinence even prior to its surgical treatment.


Protecting the blood supply from emerging pathogens: the role of pathogen inactivation.
Although the risk of infection by blood transfusion is relatively low, breakthrough infections still occur, Transfusion-related fatalities caused by infections continue to be reported, and blood is not tested for many potentially dangerous pathogens. The current paradigm for increasing the safety of the blood supply is the development and implementation of laboratory screening methods and restrictive donor criteria. When considering the large number of known pathogens and the fact that pathogens continue to emerge, it is clear that the utility of new tests and donor restrictions will continue to be a challenge when considering the cost of developing and implementing new screening assays, the loss of potential donors, and the risk of testing errors. Despite improving the safety of blood components, testing remains a reactive approach to blood safety. The contaminating organisms must be identified before sensitive tests can be developed. In contrast, pathogen inactivation is a proactive strategy designed to inactivate a pathogen before it enters the blood supply. Almost all pathogen inactivation technologies target nucleic acids, allowing for the inactivation of a variety of nucleic acid-containing pathogens within plasma, platelets, or red blood cells thus providing the potential to reduce transfusion-transmitted diseases. However, widespread use of a pathogen inactivation technology can only be realized when proven safe and efficacious and not cost-prohibitive.


Evidence of a causal role of winter virus infection during infancy in early childhood asthma.
Bronchiolitis during infancy is associated with an increased risk of childhood asthma. Whether winter viral infections cause asthma or are a manifestation of a predisposition to asthma development is unknown. To study the relationship of winter virus infection during infancy and the development of childhood asthma. We studied over 95,000 infants born between 1995 and 2000 and followed through 2005 who were enrolled in the Tennessee Medicaid program from birth through early childhood to determine whether infant birth in relationship to the winter virus peak alters the risk of developing early childhood asthma. Among 95,310 children studied during five winter virus seasons from birth through early childhood, the risk of developing asthma tracked with the timing of infant birth in relationship to the winter virus peak. Infant birth approximately 4 months before the winter virus peak carried the highest risk, with a 29% increase in odds of developing asthma compared with birth 12 months before the peak (adjusted odds ratio, 1.29; 95% confidence interval, 1.19-1.40). Infant age at the winter virus peak was comparable to or greater than other known risk factors for asthma. Timing of birth in relationship to winter virus season confers a differential and definable risk of developing early childhood asthma, establishing winter virus seasonality as a causal factor in asthma development. Delay of exposure or prevention of winter viral infection during early infancy could prevent asthma.


A comparative analysis of the principal component analysis and entropy weight methods to establish the indexing measurement.
As the world's largest coal producer, China was accounted for about 46% of global coal production. Among present coal mining risks, methane gas (called gas in this paper) explosion or ignition in an underground mine remains ever-present. Although many techniques have been used, gas accidents associated with the complex elements of underground gassy mines need more robust monitoring or warning systems to identify risks. This paper aimed to determine which single method between the PCA and Entropy methods better establishes a responsive weighted indexing measurement to improve coal mining safety. Qualitative and quantitative mixed research methodologies were adopted for this research, including analysis of two case studies, correlation analysis, and comparative analysis. The literature reviewed the most-used multi-criteria decision making (MCDM) methods, including subjective methods and objective methods. The advantages and disadvantages of each MCDM method were briefly discussed. One more round literature review was conducted to search publications between 2017 and 2019 in CNKI. Followed two case studies, correlation analysis and comparative analysis were then conducted. Research ethics was approved by the Shanxi Coking Coal Group Research Committee. The literature searched a total of 25,831publications and found that the PCA method was the predominant method adopted, and the Entropy method was the second most widely adopted method. Two weighting methods were compared using two case studies. For the comparative analysis of Case Study 1, the PCA method appeared to be more responsive than the Entropy. For Case Study 2, the Entropy method is more responsive than the PCA. As a result, both methods were adopted for different cases in the case study mine and finally deployed for user acceptance testing on 5 November 2020. The findings and suggestions were provided as further scopes for further research. This research indicated that no single method could be adopted as the better option for establishing indexing measurement in all cases. The practical implication suggests that comparative analysis should always be conducted on each case and determine the appropriate weighting method to the relevant case. This research recommended that the PCA method was a dimension reduction technique that could be handy for identifying the critical variables or factors and effectively used in hazard, risk, and emergency assessment. The PCA method might also be well-applied for developing predicting and forecasting systems as it was sensitive to outliers. The Entropy method might be suitable for all the cases requiring the MCDM. There is also a need to conduct further research to probe the causal reasons why the PCA and Entropy methods were applied to each case and not the other way round. This research found that the Entropy method provides higher accuracy than the PCA method. This research also found that the Entropy method demonstrated to assess the weights of the higher dimension dataset was higher sensitivity than the lower dimensions. Finally, the comprehensive analysis indicates a need to explore a more responsive method for establishing a weighted indexing measurement for warning applications in hazard, risk, and emergency assessments.


Inhibition of mast cell histamine release by flavonoids and biflavonoids.
The effect of 11 flavonoids and 4 biflavonoids on the release of histamine from peritoneal rat mast cells induced by compound 48/80 and calcium ionophore A23187 was studied. Dihydroflavonoids (flavanones) and (+)-catechin did not modify histamine release induced by both secretagogues. Flavone, apigenin and cromoglycate inhibited the secretion elicited by compound 48/80 but did not modify the A23187-induced secretion. The effect of kaempferol on the compound 48/80-induced histamine release was biphasic. Low doses (10 (-6) to 10 (-5)M) of the compound potentiated secretion whereas higher doses inhibited histamine secretion. Some of the drugs tested revealed a higher potency as referred to quercetin. Luteolin, a tetrahydroxyflavone and amentoflavone, a biapigenin, exhibited the highest inhibitory effects of mast cell histamine secretion.


Ophthalmic examination of the captive western lowland gorilla (Gorilla gorilla gorilla).
This study examined the captive western lowland gorilla (Gorilla gorilla gorilla) eye as compared and contrasted with the human eye. Bilateral ophthalmic examinations of western lowland gorillas (n = 5) while under general anesthesia were performed opportunistically, including slit-lamp biomicroscopy, dilated fundus examination, cycloplegic retinoscopy, Schiotz tonometry, corneal diameter and thickness measurements, A-scan and B-scan ultrasonography, keratometry, and cultures of the eyelid margins and bulbar conjunctiva. Mean spherical equivalent refractive error by cycloplegic retinoscopy was +1.20 +/- 0.59 diopters. Mean intraocular pressure by Schiotz tonometry was 12.0 +/- 4.3 mm Hg. Mean optic nerve head cup to disc ratio was 0.42 +/- 0.11. Mean horizontal corneal diameter was 13.4 +/- 0.8 mm, and mean vertical cornea diameter was 12.7 +/- 0.8 mm. Mean central corneal thickness by ultrasound pachymetry was 489 +/- 52 microm. Mean axial length of the eye by A-scan was 22.75 +/- 0.71 mm. Mean lens thickness by A-scan was 4.23 +/- 0.34 mm. Mean anterior chamber depth by A-scan was 4.00 +/- 0.26 mm. Mean keratometry reading was 44.38 +/- 1.64 diopters. Eyelid margin and bulbar conjunctival cultures isolated Candida sp. (n = 5), Staphylococcus aureus (n = 4), Staphylococcus epidermidis (n = 3), Staphylococcus saccharolyticus (n = 3), and Micrococcus sp. (n = 3). This study suggests important similarities between western lowland gorilla and human eyes. These similarities may allow diagnostics, techniques, and equipment for human eye surgery, such as those used for cataract extraction and intraocular lens implantation, to be successfully utilized for gorillas.


A reflective polarizer-free electro-optical switch using dye-doped polymer-stabilized blue phase liquid crystals.
We demonstrate a reflective polarizer-free electro-optical switch using dye-doped polymer-stabilized blue phase liquid crystals (DDPSBP-LC). At the voltage-off state, the dye molecules and liquid crystals form the structure of the double twist cylinders. As a result, the DDPSBP-LC is in dark state due to the combination of Bragg reflection and light absorption. At the voltage-on state, the blue phase structure is unwound locally. The DDPSBP-LC is then in bright state because of the small light absorption only. The applications of such a switch are shutter glass of 3D displays, and electronic papers.


Hospital space interpreted according to Heidegger's concepts of care and dwelling.
Modern hospitals have succeeded in saving humans from numerous diseases owing to the rapid development of medical technology. However, modern medical science, combined with advanced technology, has developed a strong tendency to view human beings as mere targets of restoration and repair, with modern hospitals characterised as spaces centred on technology-focused treatment. This results in a situation where human beings are reduced to objects and alienated. This study, integrating Heidegger's concepts of dwelling and care, contends that 'care' is a vital concept in terms of the fundamental spatiality of hospitals and needs to be restored as the key guiding principle affecting hospital space. The loss of the caring spirit in the development of modern hospitals affects how hospitals are conceived, built and managed, as well as how human experiences within hospitals are dealt with or allowed for appropriately. This study offers critical reflection on how future planning of hospital spaces can be better conducted to ensure that human experiences, and the care needed to appropriately value such experiences, are adequately expressed, and the complexity of human existence is suitably considered.


[Clinical usefulness and diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin].
In the context of increasing non-invasive diagnostic techniques the purpose of the present study was to determine the clinical usefulness and the diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin. 100 patients from the outpatient clinic of the department of gastroenterology and hepatology who had a liver biopsy in the years 1996 to 1998 because of chronically elevated alanine-aminotransferase (ALT) and/or gamma-glutamyltransferase (gamma-GT) levels were included. Exclusion criteria were as follows: chronic hepatitis B or C infection, focal liver disease and clinical signs of hepatic decompensation. Retrospectively gained clinical data were independently evaluated by two experienced hepatologists. Initially, both examiners made a preliminary clinical diagnosis prior to knowing results from liver histology. With the results from liver histology both examiners were asked to make a final diagnosis. For each patient, the preliminary clinical diagnoses of both examiners were then correlated with the corresponding final diagnoses. Liver histology led in 71 % respectively 74 % of the patients to confirmation or specification of the clinical diagnosis. Liver biopsy was particularly helpful in differentiating non-decompensated liver cirrhosis, cryptogenic hepatitis, auto-immune hepatitis and biliary diseases. Despite improved non-invasive diagnostic tools including a broad spectrum of serologic tests liver biopsy is often indispensable for differentiating primary liver from biliary diseases and for the early detection of patients with liver cirrhosis.


Short-Term Outcomes with Direct Aortic Access for Transcatheter Aortic Valve Replacement.
Transcatheter aortic valve replacement (TAVR) requires a safe route of access to the aortic valve. A direct aortic route has been used as alternate access approach in patients where ileo-femoral access is unsafe due to size, calcification and/or tortuosity. The study aim was to review the authors' results obtained with a direct aortic (DA) TAVR, examining in particular the safety and effectiveness of this approach. A retrospective analysis was performed of all prospectively collected TAVR data from January 2011 to March 2015 at the authors' institution. DA-TAVRs were performed using either an upper mini- sternotomy (MST) into the second right intercostal space, or via a right anterior mini-thoracotomy (RAT) at the second intercostal space. The choice between MST and RAT approaches was made by the surgeon, based on aortic imaging, patent bypass grafts and pulmonary function. Both, Medtronic CoreValve and Edwards SAPIEN devices were used. All relevant perioperative and clinical outcomes were collected based on Valve Academic Research Consortium 2 (VARC-2) definitions. Median numerical values were used. Seventy-eight consecutive patients underwent DA-TAVR with 100% intraoperative survival and 92% 30-day survival. The procedural success was 97%. The majority of patients (79%) underwent DA-TAVR with the Medtronic CoreValve, via MST (92%). All patients were classified either as extreme (74%) or high risk (26%) for surgical aortic valve replacement. DA-TAVR provides a safe and viable alternate access approach for patients with inadequate ileo-femoral access. The clinical outcomes were acceptable in this very high-risk group of patients.


Association between polymorphisms in sex hormones synthesis and metabolism and prostate cancer aggressiveness.
Novel biomarkers for prostate cancer (PCa) diagnosis and prognosis are necessary to improve the accuracy of current ones employed in clinic. We performed a retrospective study between the association of several polymorphisms in the main genes involved in the synthesis and metabolism of sex hormones and PCa risk and aggressiveness. A total of 311 Caucasian men (155 controls and 156 patients) were genotyped for 9 SNPs in AR, CYP17A1, LHCGR, ESR1 and ESR2 genes. Diagnostic PSA serum levels, Gleason score, tumor stage, D´Amico risk and data of clinical progression were obtained for patients at the moment of the diagnosis and after 54 months of follow-up. Chi-squared test were used for comparisons between clinical variables groups, logistic regression for clinical variables associations between SNPs; and Kaplan-Meier for the association between SNPs and time to biochemical progression. We found 5 variants (CYP17A1) rs743572, rs6162, rs6163; (LHCGR) rs2293275 and (ESR2) rs1256049 that were statistically significant according to clinical variables (PSA, D´Amico risk and T stage) on a case-case analysis. Moreover, the presence of A and G alleles in rs743572 and rs6162 respectively, increase the risk of higher PSA levels (>10 ng/μl). With respect to D´Amico risk rs743572 (AG-GG), rs6162 (AG-AA) and rs6163 (AC-AA) were associated with an increased risk; and last, AC and AA genotypes for rs6163 were associated with a shorter biochemical recurrence free survival (BRFS) in patients with radical prostatectomy. In multigene analysis, several variants in SNPs rs2293275, rs6152, rs1062577, rs6162, rs6163, rs1256049 and rs1004467 were described to be associated with a more aggressiveness in patients. However, none of the selected SNPs show significant values between patients and controls. In conclusion, this study identified inherited variants in genes CYP17A1, LHCGR and ESR2 related to more aggressiveness and/or a poor progression of the disease. According to this study, new promise PCa biomarkers for clinical management could be included in these previous SNPs.


Development of T cell precursor activity in the murine fetal liver.
The generation of T cell precursors in the liver of murine embryos was studied. The total number of T cell precursors in the liver was measured in thymic organ cultures by a limiting dilution assay. Sixty T cell precursors were detected in the liver at day 11 of gestation. By day 12 the number of precursors showed a 20-fold increase, half of which could be explained by in situ proliferation as ascertained by a fetal liver organ culture assay. By day 13 a further 2-3-fold increase was observed. Whereas the number of total liver cells continued to increase, that of T cell precursors declined in the following days, suggesting a massive exit of these cells after day 13. The capacity to generate a TCRB repertoire in the cells was evaluated by a PCR assay. T cell precursors in day 11 fetal liver developed a TCRB repertoire at day 8 of culture. The cells from days 12-15 developed an identically diverse repertoire by day 6, suggesting that day 11 precursors are more immature than those of later days. A mechanism for yielding a single wave of T cell precursors in the fetal liver is discussed with a proposed model.


Effects of upper respiratory tract illnesses on mood and performance over the working day.
The present study examined whether volunteers with common colds showed impairments in objective and subjective indicators of alertness over the course of the working day. All the volunteers (n = 21) were tested when healthy to provide baseline data for simple and choice reaction time tasks, visual search tasks and ratings of mood. These measures were taken before work (08.30 hours), at lunchtime (13.00) and after work (17.30). When participants developed a cold (n = 6) they repeated the procedure. Volunteers (n = 15) who remained healthy were recalled as controls and also repeated the procedures. The results showed that those with colds had significantly slower simple and choice reaction times, and felt less alert, more tense and less sociable. The effects of having a cold on simple reaction time, alertness and anxiety increased over the day. This extends earlier research and shows that some of the effects of upper respiratory tract illnesses on mood and performance will depend on when assessments are made. These results also imply that performance and well-being at work will be impaired by upper respiratory tract illnesses.


Improvement in Care and Maintenance of Port-A-Cath Following the Introduction of Care" Bundle.
Port-a-cath is a type of indwelling central venous catheter used to manage pediatric patients who require long-term intravenous therapy. The objective of this study was to improve the care and maintenance of port-a-cath among the nursing staff by introducing a care bundle. Pretraining and posttraining designs using PDSA (Plan, Do, Study, Act.) model were followed. We observed two sets of 30 procedures for accessing of port-a-cath by the nursing staff. Following the initial 30 observations of port-a-cath handling, a "care bundle" was designed as per the set standards of the maintenance of port-a-cath. It involved education and training and live audio-visual sessions. Two months after the initiation of the care bundle, the second set of 30 procedures was observed. Following the introduction of the care bundle, the observed efficacy on obtaining verbal consent improved to 100% from 83%, arrangement of drugs and instruments before insertion to 100% from 90%, not touching the needle while inserting from 60%, administration of adequate amount saline flush from 83.3% (25/30), heparin administration from 71.1%, and looking out for signs of extravasation to 100% from 80%. Two nursing staff involvement improved from 23% to 63%. A 100% efficacy in the management of nonbleeding back scenarios was observed. The cross-checking of drug expiry improved from an initial 26.6% to 89.3%. The port-a-cath infections have significantly come down (3 vs. 0) (P < 0.05). Implementation of a "care bundle" has significantly improved the quality of handling of port-a-cath and reduction in infections.


Elevated serum levels of stromal-derived factor-1alpha are associated with increased osteoclast activity and osteolytic bone disease in multiple myeloma patients.
Multiple myeloma (MM) is an incurable plasma cell (PC) malignancy able to mediate massive destruction of the axial and craniofacial skeleton. The aim of this study was to investigate the role of the potent chemokine, stromal-derived factor-1alpha (SDF-1alpha) in the recruitment of osteoclast precursors to the bone marrow. Our studies show that MM PC produce significant levels of SDF-1alpha protein and exhibit elevated plasma levels of SDF-1alpha when compared with normal, age-matched subjects. The level of SDF-1alpha positively correlated with the presence of multiple radiological bone lesions in individuals with MM, suggesting a potential role for SDF-1alpha in osteoclast precursor recruitment and activation. To examine this further, peripheral blood-derived CD14+ osteoclast precursors were cultured in an in vitro osteoclast-potentiating culture system in the presence of recombinant human SDF-1alpha. Although failing to stimulate an increase in TRAP+, multinucleated osteoclast formation, our studies show that SDF-1alpha mediated a dramatic increase in both the number and the size of the resorption lacunae formed. The increased osteoclast motility and activation in response to SDF-1alpha was associated with an increase in the expression of a number of osteoclast activation-related genes, including RANKL, RANK, TRAP, MMP-9, CA-II, and Cathepsin K. Importantly, the small-molecule CXCR4-specific inhibitor, 4F-Benzoyl-TE14011 (T140), effectively blocked osteoclast formation stimulated by the myeloma cell line, RPMI-8226. Based on these findings, we believe that the synthesis of high levels of SDF-1alpha by MM PC may serve to recruit osteoclast precursors to local sites within the bone marrow and enhance their motility and bone-resorbing activity. Therefore, we propose that inhibition of the CXCR4-SDF-1alpha axis may provide an effective means of treatment for MM-induced osteolysis.


Field-scale remediation of atrazine-contaminated soil using recombinant Escherichia coli expressing atrazine chlorohydrolase.
We performed the first field-scale atrazine remediation study in the United States using chemically killed, recombinant organisms. This field study compared biostimulation methods for enhancing atrazine degradation with a novel bioaugmentation protocol using a killed and stabilized whole-cell suspension of recombinant Escherichia coli engineered to overproduce atrazine chlorohyrolase, AtzA. AtzA dechlorinates atrazine, producing non-toxic and non-phytotoxic hydroxyatrazine. Soil contaminated by an accidental spill of atrazine (up to 29,000 p.p.m.) supported significant populations of indigenous microorganisms capable of atrazine catabolism. Laboratory experiments indicated that supplementing soil with carbon inhibited atrazine biodegradation, but inorganic phosphate stimulated atrazine biodegradation. A subsequent field-scale study consisting of nine (0.75m3) treatment plots was designed to test four treatment protocols in triplicate. Control plots contained moistened soil; biostimulation plots received 300p.p.m. phosphate; bioaugmentation plots received 0.5% (w/w) killed, recombinant E. coli cells encapsulating AtzA; and combination plots received phosphate plus the enzyme-containing cells. After 8 weeks, atrazine levels declined 52% in plots containing killed recombinant E. coli cells, and 77% in combination plots. In contrast, atrazine levels in control and biostimulation plots did not decline significantly. These data indicate that genetically engineered bacteria overexpressing catabolic genes significantly increased degradation in this soil heavily contaminated with atrazine.


Neuronal Encoding of Multisensory Motion Features in the Rat Associative Parietal Cortex.
Motion perception is facilitated by the interplay of various sensory channels. In rodents, the cortical areas involved in multisensory motion coding remain to be identified. Using voltage-sensitive-dye imaging, we revealed a visuo-tactile convergent region that anatomically corresponds to the associative parietal cortex (APC). Single unit responses to moving visual gratings or whiskers deflections revealed a specific coding of motion characteristics strikingly found in both sensory modalities. The heteromodality of this region was further supported by a large proportion of bimodal neurons and by a classification procedure revealing that APC carries information about motion features, sensory origin and multisensory direction-congruency. Altogether, the results point to a central role of APC in multisensory integration for motion perception.


Enhanced Functionality of Dual-Gate Organic Transistors Based on Semiconducting/Insulating Polyblend-Induced Asymmetric Charge Modulation Layers.
Dual-gate organic thin-film transistors (DG-OTFTs) with enhanced functionality, including large current enhancement behavior, highly efficient threshold voltage controllability, and self-contained dual-mode logic gate features, are reported. These DG-OTFTs are based on a semiconducting/insulating polyblend-based active layer with asymmetric top and bottom charge modulation layers (atb-CMLs). The atb-CMLs are automatically generated through the preparation of multilayer stacks of phase-separated semiconducting poly(3-hexylthiophene) (P3HT):insulating poly(methylmethacrylate) (PMMA) polyblend layer, poly(vinylidene fluoride) (PVDF) layer, and cross-linked-poly(4-vinylphenol) (cPVP) layer. They consist of a thin PMMA bottom layer and an uneven-shaped PMMA:PVDF miscible mixture-based top layer. The presence of the polarizable insulating PMMA, PVDF, and PMMA:PVDF mixture regions causes the bottom and top CMLs to experience electrical polarization, which induces the dipole field to achieve efficient charge modulation functions in DG-OTFTs. Owing to the presence of atb-CMLs, the DG-OTFTs exhibit unprecedented electrical characteristics, such as the easy depletion of the bottom channel by the top gate potential. However, the top channel can work properly only when given a bottom gate potential (either positive or negative). Given these unusual electrical features, the design of the fundamental dual-mode logic gates (e.g., AND and OR gates) can be achieved with just one DG transistor. This finding opens an interesting direction for the preparation of DG-OTFTs with diverse operating modes and increasing functionality, thereby widening the application potential of such transistors.


[Reoperation of tumors of the parotid gland, surgical approach and consequences for the 7th cranial nerve. Apropos of 42 cases].
Second or more surgical procedures on parotid are usually difficult and may induce injury on the facial nerve. The authors report their experience about 42 patients. The choice between a total parotidectomy or a surgical excision of a tumor depends on the number of surgical procedure, the type of initial procedure and the histological type of the tumor. Second surgical procedures for a wrong initial diagnosis (11 cases) were always a total parotidectomy with facial nerve preservation. The risk of a partial or total facial palsy is higher after several recurrences (3 of 8 cases). The facial nerve had to be resected in 3 of 9 cases of malignant tumors recurrences. The initial treatment of a tumor of the parotid must be radical so it can prevent for further surgical procedures and then avoid a facial nerve injury.


Alpha-fetoprotein in the woodchuck model of hepadnavirus infection and disease: normal physiological patterns and responses to woodchuck hepatitis virus infection and hepatocellular carcinoma.
Persistent infection of the eastern woodchuck (Marmota monax) with the woodchuck hepatitis virus (WHV) produces disease sequelae similar to those observed in humans with persistent hepatitis B virus infection, including hepatocellular carcinoma (HCC). To further characterize serological markers of HCC in the woodchuck, serum alpha-fetoprotein (AFP) was measured under normal physiological conditions and following infection with WHV. Serum AFP was elevated in association with WHV-induced hepatitis and HCC and was a useful indicator of hepatic responses in individual animals throughout the course of experimental WHV infection. The frequent occurrence of normal elevations in serum AFP during the fall and winter, however, limits the use of AFP as a marker for early detection of HCC. The present temporal studies of AFP responses in WHV-infected woodchucks have identified several stages of infection where virological and cellular interactions can be investigated at the molecular level. Studies of AFP in the woodchuck model should provide opportunities to further elucidate the physiological and immunological functions of AFP and to understand virus-host cell interactions during the course of experimental hepadnavirus infection leading to HCC.


Grade 2 Chondrosarcoma of the Great Toe: An Unusual Location.
Enchondroma is the most common benign cartilage bone tumor of the toes. In contrast, the foot is a rare region for chondrosarcoma, and the involvement of phalanges is extremely rare. In this article, we report an unusual case of intermediate chondrosarcoma involving the proximal phalanx of the great toe of a 52-year-old woman who was previously treated with curettage and bone grafting because of misinterpretation of enchondroma at a local hospital. She presented complaining of pain and swelling that she had experienced for a period of 1 year after the first operation. Radiography revealed a lytic lesion with a subtle punctuate calcification and endosteal scalloping in the proximal phalanx of the great toe. Gadolinium-enhanced magnetic resonance imaging confirmed soft-tissue involvement and cortical destruction. Staging evaluation with computed tomographic scan of the chest, abdomen, and pelvis was performed to ensure that there was no metastatic disease. Subsequently, a bone biopsy was performed, and the diagnosis was grade 2 chondrosarcoma. The patient was informed about the recurrence of the lesion and the clinical context on the basis of tumor biology of chondrosarcoma and was offered the option of either amputation or wide resection. She preferred the latter. The patient was treated with wide resection and underwent reconstruction with cement and Kirschner wire. She remains free of disease after 1 year of follow-up.


Psychopathology and adversities from early- to late-adolescence: a general population follow-up study with the CBCL DSM-Oriented Scales.
Aims. Adolescence is a critical transition phase between childhood and adulthood, when the burden of mental disorder may still be prevented. The aim of this study was to evaluate the continuity and discontinuity of behavioural problems in adolescence while taking into account the multiple co-variation of psychopathological traits and the complex role of recent stressful life events (SLEs). Methods. This is a 5-year follow-up investigation of emotional and behavioural problems assessed by the newly developed Child Behavior Checklist (CBCL) DSM-Oriented Scales (DOSs) in 420 general population subjects aged 15-19 years. Results. The DOSs showed good stability, even when multiple co-variation was taken into account. Longitudinal data showed that homotypic evolution of psychopathology was to be expected in the first place. Equifinality and multifinality were also found. Oppositional Defiant Problems emerged to be polyvalent predictors of both internalizing and externalizing problems. Furthermore, Oppositional Defiant Problems predicted more SLEs, which in turn predicted more Depression, Anxiety and Oppositional Defiant Problems. Mediational analyses confirmed the role of SLEs in partially accounting for the continuity of Oppositional Defiant Problems and for the heterotypic progression towards Affective Problems. Conclusions. These data underscore early adolescence behavioural problems as an important focus for primary and secondary intervention.


Algorithmic complexity for short binary strings applied to psychology: a primer.
As human randomness production has come to be more closely studied and used to assess executive functions (especially inhibition), many normative measures for assessing the degree to which a sequence is randomlike have been suggested. However, each of these measures focuses on one feature of randomness, leading researchers to have to use multiple measures. Although algorithmic complexity has been suggested as a means for overcoming this inconvenience, it has never been used, because standard Kolmogorov complexity is inapplicable to short strings (e.g., of length l ≤ 50), due to both computational and theoretical limitations. Here, we describe a novel technique (the coding theorem method) based on the calculation of a universal distribution, which yields an objective and universal measure of algorithmic complexity for short strings that approximates Kolmogorov-Chaitin complexity.


Overview on nutritional issues in bariatric surgery.
In the context of the worldwide obesity epidemic, bariatric surgery is the only therapy associated with a sustainable weight loss and to midterm prevention of obesity-related complications. However, nutritional and behavioral multidisciplinary medical preparation, as well as long-term postoperative nutritional follow-up, is strongly advised to avoid postoperative surgical, nutritional, or psychiatric complications. Due to a long history of restrictive diets and large body weight fluctuations, preoperative nutritional assessment and correction of vitamin and trace elements deficiencies are mandatory. A rapid and massive weight loss induces the loss of muscle mass and fat-free mass that could lead to malnutrition and osteoporosis. Dietetic counseling is advised to prevent postoperative food intolerance syndrome, malnutrition, and weight regain. Protein intake should be at least 60 g/day. Planned and structured physical exercise should be systematically promoted to maintain muscle mass and bone health. Bariatric surgery is mostly successful if patients are well prepared and monitored. The perfect patients' selection remains difficult in the absence of well defined predictive criteria of success. Future research is needed to define optimal perioperative nutritional management and its influence on long-term outcome, including quality of life and healthcare-related costs.


First Report on Resistance to HPPD Herbicides Mediated by Nontarget-Site Mechanisms in the Grass Leptochloa chinensis.
The emergence of 4-hydroxyphenylpyruvate dioxygenase (HPPD) herbicides as efficacious target-site herbicides has been noteworthy. In recent years, only four species of broadleaf weeds have developed resistance due to the long-term widespread use of HPPD herbicides. This study represents the first reported instance of a grass weed exhibiting resistance to HPPD inhibitors. We identified a new HPPD-resistant Chinese sprangletop [Leptochloa chinensis (L.) Nees] population (R population). At the recommended dose of tripyrasulfone, the inhibition rate of the R population was only half that of the sensitive population (S). The mechanism underlying resistance does not involve target-site resistance triggered by amino acid mutations or depend on disparities within the HPPD INHIBITOR SENSITIVE 1 (HIS1) gene. The impetus for resistance appears to be interlinked with the metabolic activities of cytochrome P450 monooxygenase (P450) and glutathione S-transferase (GST) family genes. Following RNA sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) validation, the study suggests that five P450 genes, CYP71C1, CYP74A2, CYP72A1, CYP84A1, and CYP714C2, alongside a single GST gene GSTF1, may be implicated in the process of metabolic detoxification.


Combined aerobic and resistance training decreases inflammation markers in healthy men.
Our primary aim was to study the effects of 24 weeks of combined aerobic and resistance training performed on the same day or on different days on inflammation markers. Physically active, healthy young men were randomly divided into three groups that performed: aerobic and resistance training consecutively in the same training session (SS) 2-3 days wk-1 or on alternating days (AD) 4-6 days wk-1 as well as control (C). The total training volume was matched in the training groups. The control group was asked to maintain their habitual physical activity and exercise level. Maximal leg press strength (1RM) and peak oxygen uptake (VO2peak ) were measured. Abdominal fat mass was estimated with dual-energy absorptiometry (DXA). High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), and adipocytokines resistin, adiponectin, and leptin were analyzed from plasma samples. Training significantly reduced circulating hs-CRP, leptin, and resistin in both training groups (P<.05), whereas MCP-1 and TNF-α decreased only in AD (P<.05). Significant correlations were observed between changes in abdominal fat mass and corresponding changes in MCP-1, leptin, adiponectin, and resistin. Long-term combined aerobic and resistance training reduced markers of subclinical inflammation in healthy young men. The results indicate that a higher frequency of individual exercise sessions might be more beneficial with respect to the anti-inflammatory effects of physical activity. The decreases in inflammation markers seem to be related to decreases in abdominal fat mass.


Bone graft materials for posterolateral fusion made simple: a systematic review.
Iliac crest has long been the gold standard for lumbar fusion, but concerns over donor site morbidity have led to a wide variety of bone graft substitutes. Despite prolific research, a general consensus is yet to be reached on bone graft materials that lead to optimal fusion. The purpose of this review is to evaluate the current literature for bone graft material options that maximize fusion rate in posterolateral lumbar fusion surgery. Systematic Review. A PRISMA-compliant systematic review of PubMed, EMBASE, and the Web of Science was conducted. Included studies were published from January 2000 to July 2015, were clinical human research studies involving available autograft, allograft, or synthetic bone graft options in posterolateral lumbar spine fusion, and reported radiographic fusion rate as a primary end outcome. This research had no funding source and the authors have no conflicts to declare. 81 articles underwent full-text review, and 48 were included in this study. 18 studies assessed fusion rate by plain radiographs alone (37.5%), while 6 used CT scan (12.5%), and 24 used both (50.0%). 45 studies looked at ICBG in conjunction with LAG (29), BCP(1), APC (2), BMPs (6), or DBM (1). Aggregate mean fusion rates among these ranged from 68.0 to 91.5%. 22 studies evaluated fusion rates of LAG, either isolated (3) or combined with ceramic extenders (8), DBM (4), BMP (1), BMA (4), APC (1), or ICBG(1). Aggregate mean fusion rate ranged from 75 to 95.5%. With the exception of studies involving allograft (mean fusion rate 40.0%), the mean fusion rate for all other graft combinations exceeded 70.0%. While our results find that LAG+BMA provided highest fusion rate, most material options analyzed in this study provide comparable fusion outcomes. The ideal graft option must incorporate a combination of materials with osteoconductive, osteoinductive, and osteogenic properties. Our results represent the robust and dynamic nature of the current state of lumbar graft technology. These slides can be retrieved under Electronic Supplementary Material.


Tumor lysis syndrome: a systematic review of case series and case reports.
Tumor lysis syndrome (TLS) is a clinical condition that is caused by a massive lysis of tumor cells that accumulate very rapidly and disturb hemodynamics. This oncologic emergency requires immediate intervention. Tumor lysis syndrome was first described in the 19th century. Since then, it has become a well-known disease with improved management measures. Tumor lysis syndrome can occur after any type of neoplasm. It is highly associated with rapidly proliferating tumors compared with those that are well demarcated, such as acute lymphoblastic leukemia and high-grade non-Hodgkin lymphoma. Initiation of chemotherapy, radiotherapy, or steroid treatment may trigger TLS, or it may develop spontaneously. The release of massive quantities of intracellular contents may produce hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute renal failure. Prevention and treatment measures include intravenous hydration, use of allopurinol and rasburicase, management of TLS-associated electrolyte abnormalities, and renal replacement therapy; the use of urine alkalinization remains controversial. In this article, we summarize the findings of case series and case reports published over the past 6 years in an effort to help familiarize clinicians better recognize and manage TLS.


Sub-micrometer Sized, 3D-Surface-attached Polymer Networks by Microcontact Printing: Using UV-Crosslinking Efficiency to Tune Structure Height.
The lateral dimensions of micro- and nanostructures obtained by microcontact printing (μCP) can be easily varied by selecting stamps with the desired spacing and pattern. However, the height of these structures cannot be tuned as easily, and in most cases only 2D structures are obtained. Here, we show how the chemical cross-linking properties of polymer inks designed for μCP can be used to obtain 3D structures with heights ranging from 3 to 750 nm using the same μCP stamps. This is technologically relevant because the ink concentration affects the quality and resolution of the printed image, and therefore can only be varied in a certain range. By exploiting the cross-linking efficiency to tune the height, an additional parameter is available to reach the desired structure height without compromising the image quality. The inks were made from copolymers containing a low percentage of different UV cross-linkable repeat units: nitrobenzoxadiazole (NBD), coumarin (COU), and/or benzophenone (BP). The base polymer of the here presented model system was an antimicrobially active poly(oxanorbornene) (SMAMP), however the concept should be transferable to many other polymer backbones. We describe the fabrication and characterization of the printed micro- and nanostructures made from pure SMAMP, NBD-SMAMP, coumarin-SMAMP, BP-SMAMP, BP-NBD-SMAMP and BP-coumarin-SMAMP polymer inks. The photo-dimerization of COU during UV irradiation at λ = 254 nm was confirmed by UV-Vis spectroscopy. Since NBD and COU are fluorescent, the polymer could be visualized by fluorescence microscopy. Additionally, their height profiles were measured by atomic force microscopy (AFM). The heights of the 3D surface-attached polymer networks obtained from the here presented polymer inks correlated with the gel-content of the corresponding unstructured polymer layers, and thus with the cross-linking efficiency of the NBD, COU and BP cross-linkers. Due to being covalently cross-linked, these 3D-surface attached polymer structures were solvent-stable and stable in aqueous surroundings.


Effects of feed restriction on growth and metabolism of replacement pullets.
The effects of feed restriction on lipogenesis, carcass composition, and protein utilization were investigated. Two feed restriction programs were used: restricted duration of feeding (RDF) whereby pullets had access to feed for 7 or 9 hr/day and restricted access to feed (ADF) in which feed was available on alternate days. A control group received the same diet as the restricted groups but on an ad libitum basis. The feeding programs were applied to a white egg and brown egg strain of commercial laying hens from 1 until 5 weeks of age or from 3 days (RDF) or 10 weeks (ADF) until 19 weeks of age. The ADF restriction resulted in 12 to 25% decrease in body weights at 5 weeks and 5 to 11% decrease in body weights at 18 or 19 weeks. The RDF depressed body weights 24% at 5 weeks and 2% at 18 weeks. The RDF and ADF increased hepatic malic enzyme and glutamic oxaloacetic transaminase activities in both age groups. Plasma uric acid and hepatic glutamic pyruvic transaminase were affected, but not consistently, by ADF. It is hypothesized that ADF and RDF lead to increased lipogenesis and increased utilization of amino acids as sources of energy. Under conditions of mild restriction, this may result in increased carcass fat content.


An Official American Thoracic Society Workshop Report: Translational Research in Rare Respiratory Diseases.
Rare respiratory diseases (RRDs) are a heterogeneous group of disorders that collectively represent a significant health care burden. In recent years, strong advocacy and policy initiatives have led to advances in the implementation of research and clinical care for rare diseases. The development of specialized centers and research networks has facilitated support for affected individuals as well as emerging programs in basic, translational, and clinical research. In selected RRDs, subsequent gains in knowledge have informed the development of targeted therapies and effective diagnostic tests, but many gaps persist. There was therefore a desire to identify the elements contributing to an effective translational research program in RRDs. To this end, a workshop was convened in October 2015 with a focus on the implementation of effective transnational research networks and collaborations aimed at developing novel diagnostic and therapeutic tools. Key elements included an emphasis on molecular pathogenesis, the continuing engagement of patient advocacy groups and policy makers, the effective use of preclinical models in the translational research pipeline, and the detailed phenotyping of patient cohorts. During the course of the workshop, current logistical and knowledge gaps were identified, and new solutions or opportunities were highlighted.


[Asthma, allergic rhinitis, sinusitis. Concept of the "unified respiratory tracts"].
Epidemiological studies indicate that allergic rhinoconjunctivitis (ARC) is an important risk factor for bronchial asthma. Both asthma and ARC have now been recognized as inflammatory diseases with similar manifestations in the mucous membranes of the upper (nose and paranasal sinuses) and lower respiratory tract (bronchi). Recent studies show that the deposition of allergen into the lower respiratory tract leads to increased inflammation of the upper respiratory tract, even if the patients are only suffering from ARC. These and other findings indicate that allergic diseases have a systemic component, which might be insufficiently targeted with local therapy. It is currently believed that the impaired function of the upper airways due to ARC causing nasal obstruction, retention of secretions, and disturbed conditioning of the inspired air plays an important role in the development of lower airway symptoms. Studies indicate that treatment of the upper respiratory tract inflammation not only reduces the manifestation of allergen-associated symptoms in the lower respiratory tract, but might also have preventive properties if applied early. ARC should no longer be viewed as a harmless disorder but as the early manifestation of a potentially progressive systemic disease and be treated as such.


Brachial plexus traction injuries.
Brachial plexus traction injuries most frequently occur following acute flexion or extension of the neck. The symptomatology following this injury may be defined clearly into the anatomic patterns of upper trunk, lower trunk, posterior cord, medial cord, and lateral cord radiations. This injury is the most common cause of the neurogenic form of thoracic outlet syndrome and is frequently seen in conjunction with cervical spine disease as well as peripheral entrapment syndromes of the ulnar, radial, and medial nerves.


The Effects of Concentric Resistance Training on Eccentric Peak Torque and Muscle Cross-sectional Area.
This study was designed to investigate the effects of concentric resistance training on isokinetic concentric and eccentric peak torque and muscle cross-sectional area. Using a time-series design, 14 males with previous strength training experience were assigned to six weeks of control activity, followed by 12 weeks of high-resistance training of the knee extensors and flexors on variable resistance hydraulic equipment that allowed concentric contractions only. Angular velocities of movement about the knee and hip during training were maintained at approximately 1.05 rad.s-1. Peak concentric and eccentric torques of the knee extensors and flexors at 1.05 rad.s-1 were assessed three times before training and during the training program at six and 12 weeks. No significant changes in peak torque were observed over the control period. After six weeks of training, peak torque in all four tests were increased (p < .05) over pretraining values. After 12 weeks of training, torques were further increased (p < .05) over the values at the six-week point. Cross-sectional area (CSA) of the quadriceps femoris muscle and the hamstring muscle groups was measured by computerized tomography (CT) scanning techniques before training and during the program at six and 12 weeks. CSA was significantly (p < .05) increased for the quadriceps femoris muscle but not the hamstrings group after six weeks of training. After 12 weeks of training, the CSA of both muscle groups increased (p < .05) over the six-week measurement. The results of this study suggest that strength training effects are not completely specific to the contraction type utilized in training. J Orthop Sports Phys Ther 1991;13(3):132-137.


Effects of aromatic trifluoromethylation, fluorination, and methylation on intermolecular π-π interactions.
Marcus theory states that the rate of charge transfer is directly proportional to the amount of intermolecular orbital overlap. Theoretically optimizing the electronic coupling through the orientation and distance which both can increase the frontier orbital overlap between molecules is an attractive route to potentially provide theoretical insight for discovering new high performance semiconductor materials. To investigate how these parameters qualitatively affect charge transfer of model systems, unconstrained dimer optimizations with MP2 and dispersion-corrected DFT methods were used to probe the π-π interactions of methylated, fluorinated, and trifluoromethylated benzene, pyridine, and bipyridine dimers. These systems can serve as simplified models representing weak noncovalent interactions in organic semiconductor materials. Enhanced intermolecular interaction energies, reduced π-π distances, and more favorable cofacial orientations were found with the trifluoromethylated dimers compared to fluorinated and methylated dimers studied. Similar effects were found with donor-acceptor pairs that represent organic p-n heterojunction systems. These enhanced π-π interactions are likely caused by increased molecular quadrupole moment and dispersion interaction associated with trifluoromethylation. This computational study illustrates the strong potential of trifluoromethylation and, possibly perfluoroalkylation of acenes and heteroacenes, leading qualitatively to enhanced electron transfer through better π-π stacked structures, making them viable candidates for use as n-type organic semiconductor materials. The findings also provide insight for fundamental interactions between drug molecules that include fluorinated and trimethylfluorinated aromatics binding to protein receptors.


Herpes simplex virus replication and protein synthesis in a human blood-derived cell line.
Herpes simplex virus (HSV) types 1 and 2 were shown to replicate in a newly described human cell line (Meg) derived from the peripheral blood of a healthy volunteer. The cell line has both megakaryocyte-like and B cell-like properties. Upon infection with HSV-1 or -2, at a m.o.i. between 0.5 and 5, unlike B and T cells, the Meg cells were growth-arrested and this was accompanied by cytopathic effects and virus replication. The HSV proteins and glycoproteins B and D (gB and gD) made in the blood-derived Meg cells were compared to the corresponding proteins made in the non-blood-derived cell lines, Vero (African green monkey kidney cell) and HEp-2 (human epidermoid carcinoma cell). The maximum level of HSV protein synthesis occurred earlier in the Meg cells than in the Vero and HEp-2 cells. The electrophoretic pattern of HSV-1 and -2 proteins made in the Meg cell line was similar to the corresponding proteins made in the Vero and HEp-2 cell lines; however, some qualitative and quantitative differences were evident. There were no apparent differences detected in the migration pattern of gB made in all three cell lines while significant differences were observed with the gD species. However, upon hydrolysis with Staphylococcus aureus V-8 protease of the monoclonal antibody-purified gB and gD, distinct differences were observed in the electrophoretic pattern of the generated peptide fragments of both gB and gD made in the three cell lines. The results demonstrate that a human blood cell can support HSV replication and that species-specific post-translational modification of gB and gD occurs in HSV-infected Vero cells as compared to HSV-infected human cells.


Effect of pH on tobacco anionic peroxidase stability and its interaction with hydrogen peroxide.
The effect of extremely acidic pH on the stability of tobacco peroxidase and lignin peroxidase holoenzymes has been studied. Stabilization of tobacco peroxidase holoenzyme in the presence of calcium cations at pH < 2 and stabilization of lignin peroxidase at pH > 2 in the presence of veratryl alcohol have been shown. The dependence of the reaction rate constant for hydrogen peroxide interaction with tobacco peroxidase on pH suggests that the reaction rate is under control of a group with pK of 2.5. A tobacco peroxidase model structure has been created by means of homology modeling on the basis of the tobacco peroxidase sequence and the coordinates of peanut peroxidase crystal structure. The model structure demonstrates the presence of the negatively charged Glu-141 at the entrance to the active site and its electrostatic repulsion from heme propionates and triad of Asp-76, -79, and -80 residues. The results on tobacco holoperoxidase stabilization at pH 1.8 in the presence of calcium cations and drop in reaction rate constant for the enzyme interaction with hydrogen peroxide are explained by a hypothetical formation of ionic bonds between Glu-141 and the triad of aspartic acid residues via calcium cation lowering the accessibility of the active site and stabilizing the holoenzyme.


Auditing occupational medicine.
An important challenge facing the quality of practice in occupational medicine is a limited evidence-base, but equally important is the need to translate good evidence into high quality practice. Audit has an important role to play in addressing the determinants of variations in practice. Furthermore where the evidence is good enough to permit the development of valid practice guidelines, audit may help in improving education and standards of practice. External audit may have a role to play in ensuring conformity with service-level agreements and especially in addressing issues of quality which some management systems may fail to address. As more literature is published reviewing and achieving a consensus on the evidence-base for the practice of occupational medicine, and as more experience in audit is described, it can make an important contribution to quality in occupational medicine.


Stimulatory Effects of Balanced Deep Sea Water on Mitochondrial Biogenesis and Function.
The worldwide prevalence of metabolic diseases, including obesity and diabetes, is increasing. Mitochondrial dysfunction is recognized as a core feature of these diseases. Emerging evidence also suggests that defects in mitochondrial biogenesis, number, morphology, fusion, and fission, contribute to the development and progression of metabolic diseases. Our previous studies revealed that balanced deep-sea water (BDSW) has potential as a treatment for diabetes and obesity. In this study, we aimed to investigate the mechanism by which BDSW regulates diabetes and obesity by studying its effects on mitochondrial metabolism. To determine whether BDSW regulates mitochondrial biogenesis and function, we investigated its effects on mitochondrial DNA (mtDNA) content, mitochondrial enzyme activity, and the expression of transcription factors and mitochondria specific genes, as well as on the phosphorylation of signaling molecules associated with mitochondria biogenesis and its function in C2C12 myotubes. BDSW increased mitochondrial biogenesis in a time and dose-dependent manner. Quantitative real-time PCR revealed that BDSW enhances gene expression of PGC-1α, NRF1, and TFAM for mitochondrial transcription; MFN1/2 and DRP1 for mitochondrial fusion; OPA1 for mitochondrial fission; TOMM40 and TIMM44 for mitochondrial protein import; CPT-1α and MCAD for fatty acid oxidation; CYTC for oxidative phosphorylation. Upregulation of these genes was validated by increased mitochondria staining, CS activity, CytC oxidase activity, NAD+ to NADH ratio, and the phosphorylation of signaling molecules such as AMPK and SIRT1. Moreover, drinking BDSW remarkably improved mtDNA content in the muscles of HFD-induced obese mice. Taken together, these results suggest that the stimulatory effect of BDSW on mitochondrial biogenesis and function may provide further insights into the regulatory mechanism of BDSW-induced anti-diabetic and anti-obesity action.


Imputing Risk Tolerance From Survey Responses.
Economic theory assigns a central role to risk preferences. This article develops a measure of relative risk tolerance using responses to hypothetical income gambles in the Health and Retirement Study. In contrast to most survey measures that produce an ordinal metric, this article shows how to construct a cardinal proxy for the risk tolerance of each survey respondent. The article also shows how to account for measurement error in estimating this proxy and how to obtain consistent regression estimates despite the measurement error. The risk tolerance proxy is shown to explain differences in asset allocation across households.


Possible prediction of adverse reactions to fluorouracil by the measurement of urinary dihydrothymine and thymine.
Dihydropyrimidine dehydrogenase (DPD) deficiency with a defect of the pyrimidine catabolic pathway has recently become the focus of considerable attention, due to the severe 5-fluorouracil (5-FU) toxicities occurring in DPD deficiency patients. Studies also suggest that 5-FU toxicities could occur in another pyrimidine metabolic disorder, dihydropyrimidinuria (DHPuria). This study shows that urinary dihydrothymine (DHT) and thymine (THY) are useful indexes for detection of DPD deficiency and DHPuria. We measured urinary DHT and THY in 276 Japanese adults to establish reference ranges. When males and females were compared, both DHT and THY levels were found to be significantly higher in females. The reference ranges (mean +/- SD with logarithmic values) for males were found to be 1.56-5.70 micromol/g of creatinine for DHT and 0.40-1.47 micromol/g of creatinine for THY. The reference ranges for females were found to be 1.89-8.33 micromol/g of creatinine for DHT and 0.58-2.30 micromol/g of creatinine for THY. In addition to this study we analyzed a DPD deficiency case and a DHPuria case. In the DPD deficiency case, the THY concentrations of all urine samples were out of the reference range. However, uracil levels in most of the samples were within the normal range. The DHPuria case excreted large amounts of DHT and dihydrouracil, both out of the normal range.


The clinical practice guideline for the management of ARDS in Japan.
The Japanese Society of Respiratory Care Medicine and the Japanese Society of Intensive Care Medicine provide here a clinical practice guideline for the management of adult patients with ARDS in the ICU. The guideline was developed applying the GRADE system for performing robust systematic reviews with plausible recommendations. The guideline consists of 13 clinical questions mainly regarding ventilator settings and drug therapies (the last question includes 11 medications that are not approved for clinical use in Japan). The recommendations for adult patients with ARDS include: we suggest against early tracheostomy (GRADE 2C), we suggest using NPPV for early respiratory management (GRADE 2C), we recommend the use of low tidal volumes at 6-8 mL/kg (GRADE 1B), we suggest setting the plateau pressure at 30cmH20 or less (GRADE2B), we suggest using PEEP within the range of plateau pressures less than or equal to 30cmH2O, without compromising hemodynamics (Grade 2B), and using higher PEEP levels in patients with moderate to severe ARDS (Grade 2B), we suggest using protocolized methods for liberation from mechanical ventilation (Grade 2D), we suggest prone positioning especially in patients with moderate to severe respiratory dysfunction (GRADE 2C), we suggest against the use of high frequency oscillation (GRADE 2C), we suggest the use of neuromuscular blocking agents in patients requiring mechanical ventilation under certain circumstances (GRADE 2B), we suggest fluid restriction in the management of ARDS (GRADE 2A), we do not suggest the use of neutrophil elastase inhibitors (GRADE 2D), we suggest the administration of steroids, equivalent to methylprednisolone 1-2mg/kg/ day (GRADE 2A), and we do not recommend other medications for the treatment of adult patients with ARDS (GRADE1B; inhaled/intravenous β2 stimulants, prostaglandin E1, activated protein C, ketoconazole, and lisofylline, GRADE 1C; inhaled nitric oxide, GRADE 1D; surfactant, GRADE 2B; granulocyte macrophage colony-stimulating factor, N-acetylcysteine, GRADE 2C; Statin.). This article was translated from the Japanese version originally published as the ARDS clinical practice guidelines 2016 by the committee of ARDS clinical practice guideline (Tokyo, 2016, 293p, available from http://www.jsicm.org/ARDSGL/ARDSGL2016.pdf). The original article, written for Japanese healthcare providers, provides points of view that are different from those in other countries.


Abolishing activity against ascorbate in a cytosolic ascorbate peroxidase from switchgrass.
Switchgrass (Panicum virgatum L.) is being developed as a bioenergy species. Recently an early version of its genome has been released permitting a route to the cloning and analysis of key proteins. Ascorbate peroxidases (APx) are an important part of the antioxidant defense system of plant cells and present a well studied model to understand structure-function relationships. Analysis of the genome indicates that switchgrass encodes several cytosolic ascorbate peroxidases with apparent varying levels of tissue expression. A major cytosolic ascorbate peroxidase was thus selected for further studies. This gene was cloned and expressed in Escherichia coli cells to obtain purified active protein. Full heme incorporation of the enzyme was achieved utilizing slow growth and supplementing the media with 5-aminolevulinic acid. The enzyme was observed to be monomeric in solution via size exclusion chromatography. Activity toward ascorbate was observed that was non-Michaelis-Menten in nature. A site-directed mutant, R172S, was made in an attempt to differentiate activity against ascorbate versus other substrates. The R172S protein exhibited negligible ascorbate peroxidase activity, but showed near wild type activity toward other aromatic substrates.


On the accuracy of PSF representation in image restoration.
Point spread function (PSF) models derived from physical optics provide a more accurate representation of real blurs than simpler models based on geometrical optics. However, the physical PSF models do not always result in a significantly better restoration, due to the coarse sampling of the recording device and insufficiently high signal-to-noise ratio (SNR) levels. Low recording resolutions result in aliasing errors in the PSF and suboptimal restorations. A high-resolution representation of the PSF where aliasing errors are minimized is used to obtain improved restorations. The SNR is the parameter which ultimately limits the restoration quality and determines the need for an accurate PSF model. As a rule of thumb, the geometrical PSF can be used in place of the physical PSF without significant loss in restoration quality when the SNR is less than 30 dB.


Neuropsychological Recovery Trajectories in Moderate to Severe Traumatic Brain Injury: Influence of Patient Characteristics and Diffuse Axonal Injury.
The goal of the present study was to elucidate the influence of demographic and neuropathological moderators on the longitudinal trajectory neuropsychological functions during the first year after moderate to severe traumatic brain injury (TBI). In addition to examining demographic moderators such as age and education, we included a measure of whole-brain diffuse axonal injury (DAI), and examined measures of processing speed (PS), executive function (EF), and verbal learning (VL) separately. Forty-six adults with moderate to severe TBI were examined at 3, 6, and 12 months post-injury. Participants underwent neuropsychological evaluation and neuroimaging including diffusion tensor imaging. Using linear mixed effects modeling, we examined longitudinal trajectories and moderating factors of cognitive outcomes separately for three domains: PS, VL, and EF. VL and EF showed linear improvements, whereas PS exhibited a curvilinear trend characterized by initial improvements that plateaued or declined, depending on age. Age moderated the recovery trajectories of EF and PS. Education and DAI did not influence trajectory but were related to initial level of functioning for PS and EF in the case of DAI, and all three cognitive domains in the case of education. We found disparate recovery trajectories across cognitive domains. Younger age was associated with more favorable recovery of EF and PS. These findings have both clinical and theoretical implications. Future research with a larger sample followed over a longer time period is needed to further elucidate the factors that may influence cognitive change over the acute to chronic period after TBI. (JINS, 2018, 24, 237-246).


Elder abuse in nursing homes: an ecological perspective.
Population trends suggest that the next 20 years will witness a dramatic increase in the adult population aged 65 and older. Projected increases in the elderly population are expected to significantly increase the stress on family and professional caretakers. Stress, in the context of caregiving relationships, is a risk factor associated with increased prevalence of elder abuse in familial and institutional settings. As increasing numbers of older adults are moved from family caregiving to nursing home care settings, it becomes important to identify the pattern of elder abuse risk factors in nursing home facilities. An ecological model is proposed for better understanding the risk factors associated with elder abuse in nursing homes and the complex interaction of individual/person characteristics and contextual factors in institutional elder abuse. An ecological perspective to institutional elder abuse provides a framework for guiding and informing future research on the risk factors of nursing home abuse and, in turn, for the development of effective interventions and relevant social policies.


Morphological Modifications in Myofibrils by Suppressing Tropomyosin 4α in Chicken Cardiac Myocytes.
Tropomyosin (TPM) localizes along F-actin and, together with troponin T (TnT) and other components, controls calcium-sensitive muscle contraction. The role of the TPM isoform (TPM4α) that is expressed in embryonic and adult cardiac muscle cells in chicken is poorly understood. To analyze the function of TPM4α in myofibrils, the effects of TPM4α-suppression were examined in embryonic cardiomyocytes by small interference RNA transfection. Localization of myofibril proteins such as TPM, actin, TnT, α-actinin, myosin and connectin was examined by immunofluorescence microscopy on day 5 when almost complete TPM4α-suppression occurred in culture. A unique large structure was detected, consisting of an actin aggregate bulging from the actin bundle, and many curved filaments projecting from the aggregate. TPM, TnT and actin were detected on the large structure, but myosin, connectin, α-actinin and obvious myofibril striations were undetectable. It is possible that TPM4α-suppressed actin filaments are sorted and excluded at the place of the large structure. This suggests that TPM4α-suppression significantly affects actin filament, and that TPM4α plays an important role in constructing and maintaining sarcomeres and myofibrils in cardiac muscle.


Bacillus cereus and its food poisoning toxins.
Bacillus cereus is becoming one of the more important causes of food poisoning in the industrialised world. It produces one emetic toxin and three different enterotoxins. The emetic toxin is a ring-shaped structure of three repeats of four amino and/or oxy acids: [D-O-Leu-D-Ala-L-O-Val-L-Val]3. This ring structure has a molecular mass of 1.2 kDa, and is chemically closely related to the potassium ionophore valinomycin. Two of the three enterotoxins have been shown to be involved in food poisoning. They both consist of three different proteins that act together. One of these enterotoxins is also a haemolysin. This haemolytic enterotoxin is transcribed from one operon. The third enterotoxin is a single component protein, but has not been shown to be involved in food poisoning.


Hydrophobic pulses predict transmembrane helix irregularities and channel transmembrane units.
Few high-resolution structures of integral membranes proteins are available, as crystallization of such proteins needs yet to overcome too many technical limitations. Nevertheless, prediction of their transmembrane (TM) structure by bioinformatics tools provides interesting insights on the topology of these proteins. We describe here how to extract new information from the analysis of hydrophobicity variations or hydrophobic pulses (HPulses) in the sequence of integral membrane proteins using the Hydrophobic Pulse Predictor, a new tool we developed for this purpose. To analyze the primary sequence of 70 integral membrane proteins we defined two levels of analysis: G1-HPulses for sliding windows of n = 2 to 6 and G2-HPulses for sliding windows of n = 12 to 16. The G2-HPulse analysis of 541 transmembrane helices allowed the definition of the new concept of transmembrane unit (TMU) that groups together transmembrane helices and segments with potential adjacent structures. In addition, the G1-HPulse analysis identified helix irregularities that corresponded to kinks, partial helices or unannotated structural events. These irregularities could represent key dynamic elements that are alternatively activated depending on the channel status as illustrated by the crystal structures of the lactose permease in different conformations. Our results open a new way in the understanding of transmembrane secondary structures: hydrophobicity through hydrophobic pulses strongly impacts on such embedded structures and is not confined to define the transmembrane status of amino acids.


[Effect of lipid peroxidation on the insulin receptor in rat adipocytes].
Lipid peroxidation is studied for its effect on insulin receptors in isolated rat adipocytes. The results suggest that addition of two peroxidants (3 mM cumene hydroperoxide and 0.2 mM Fe2+) leads to malondialdehyde accumulation and binding inhibition through insulin receptors quantity and affinity decrease.


RPGRIP1s with distinct neuronal localization and biochemical properties associate selectively with RanBP2 in amacrine neurons.
RPGR and RPGRIP1 are molecular partners with vital roles in retinal function. Mutations in RPGR are implicated in heterogeneous retinal phenotypes, while those in RPGRIP1 lead to Leber congenital amaurosis. RPGR and RPGRIP1s differentially localize in photoreceptors among species. This may contribute to phenotype disparities among species bearing mutations in RPGR. However, it cannot account for the phenotype heterogeneity associated with RPGR- and RPGRIP1-linked mutations in the human. The existence of RPGRIP1 isoforms with distinct cellular, subcellular localizations and biochemical properties in the retina is shown. High mass RPGRIP1 isoforms, p175/p150, enriched in the outer segment (OS) compartment of photoreceptors are identified. The remaining isoforms are present across subcellular fractions, including nuclei and are soluble. The p175/p150 are predominantly sequestered in the cytoskeleton-insoluble fraction of OS and nuclei. In selective amacrine cells, and in the transformed photoreceptor line, 661W, RPGRIP1s localize at restricted foci to nuclear pore complexes and/or the vicinity of these. Among the nucleoporins, RPGRIP1 isoforms selectively associate in vivo with RanBP2 (Nup358). RPGRIP1s also decorate microtubules in 661W cells and occasionally form coiled-like inclusion bodies in the perikarya. These results support distinct but complementary functions of RPGRIP1 isoforms in cytoskeletal-mediated processes in photoreceptors and amacrine neurons, and may explain the Leber phenotype linked to RPGRIP1 mutations in humans. Moreover, the data implicate a role of RanBP2 in the pathogenesis of neuro(retino)pathies and as a docking station to mediate the nucleocytoplasmic shuttling of RPGRIP1s and their interaction with other partners in amacrine and 661W neurons.


Effect of exercise position during stress testing on cardiac and pulmonary thallium kinetics and accuracy in evaluating coronary artery disease.
We compared the effects of symptom-limited upright and supine exercise on 201Tl distribution and kinetics in the heart and lungs of 100 consecutive patients. Our analysis was based on data obtained with a digital gamma camera in the 45 degrees left anterior oblique position at 5, 40, 240, and 275 min postadministration of [201Tl]chloride. We found significant differences in the results at the 5- and 40-min intervals; viz, higher cardiac and lower pulmonary thallium activity after upright exercise in 94 subjects at both intervals, and greater variability in total and regional cardiac thallium kinetics after supine exercise. With supine exercise, the relatively low initial cardiac activity, relatively high lung activity, and the greater variability in thallium kinetics combined to make interpretation of quantitative data and cardiac images difficult and less accurate with respect to detection of coronary artery disease. These observations have important implications for the interpreting physician when thallium stress tests are performed in the supine position.


Problems with condom use among patients attending sexually transmitted disease clinics: prevalence, predictors, and relation to incident gonorrhea and chlamydia.
Condom use remains important for sexually transmitted disease (STD) prevention. This analysis examined the prevalence of problems with condoms among 1,152 participants who completed a supplemental questionnaire as part of Project RESPECT, a counseling intervention trial conducted at five publicly funded STD clinics between 1993 and 1997. Altogether, 336 participants (41%, 95% confidence interval: 38, 45) reporting condom use indicated that condoms broke, slipped off, leaked, or were not used throughout intercourse in the previous 3 months. Correspondingly, 8.9% (95% confidence interval: 7.0, 9.5) of uses resulted in STD exposure if partners were infected because of delayed application of condoms (4.3% of uses), breakage (2.0%), early removal (1.4%), slippage (1.3%), or leakage (0.4%). Use problems were significantly associated with reporting inconsistent condom use, multiple partners, and other condom problems. One-hundred thirty participants completing the questionnaire were tested for gonorrhea and chlamydia at this time and also 3 months earlier. Twenty-one (16.2%) were infected with incident gonorrhea and chlamydia, with no infections among consistent users reporting no use problems. Exact logistic regression revealed a significant dose-response relation between increased protection from condom use and reduced gonorrhea and chlamydia risk (p(trend) = 0.032). Both consistency of use and use problems must be considered in studies of highly infectious STD to avoid underestimating condom effectiveness.


N-Methyl-D-Aspartate Receptor Link to the MAP Kinase Pathway in Cortical and Hippocampal Neurons and Microglia Is Dependent on Calcium Sensors and Is Blocked by α-Synuclein, Tau, and Phospho-Tau in Non-transgenic and Transgenic APPSw,Ind Mice.
N-methyl-D-aspartate receptors (NMDARs) respond to glutamate to allow the influx of calcium ions and the signaling to the mitogen-activated protein kinase (MAPK) cascade. Both MAPK- and Ca2+-mediated events are important for both neurotransmission and neural cell function and fate. Using a heterologous expression system, we demonstrate that NMDAR may interact with the EF-hand calcium-binding proteins calmodulin, calneuron-1, and NCS1 but not with caldendrin. NMDARs were present in primary cultures of both neurons and microglia from cortex and hippocampus. Calmodulin in microglia, and calmodulin and NCS1 in neurons, are necessary for NMDA-induced MAP kinase pathway activation. Remarkably, signaling to the MAP kinase pathway was blunted in primary cultures of cortical and hippocampal neurons and microglia from wild-type animals by proteins involved in neurodegenerative diseases: α-synuclein, Tau, and p-Tau. A similar blockade by pathogenic proteins was found using samples from the APPSw,Ind transgenic Alzheimer's disease model. Interestingly, a very marked increase in NMDAR-NCS1 complexes was identified in neurons and a marked increase of both NMDAR-NCS1 and NMDAR-CaM complexes was identified in microglia from the transgenic mice. The results show that α-synuclein, Tau, and p-Tau disrupt the signaling of NMDAR to the MAPK pathway and that calcium sensors are important for NMDAR function both in neurons and microglia. Finally, it should be noted that the expression of receptor-calcium sensor complexes, specially those involving NCS1, is altered in neural cells from APPSw,Ind mouse embryos/pups.


Effects of the circadian variation in serum cortisol on markers of bone turnover and calcium homeostasis in normal postmenopausal women.
Bone turnover has a circadian pattern, with bone resorption and, to a lesser extent, bone formation increasing at night. Serum cortisol also has a circadian pattern and is a potential candidate for mediating the circadian changes in bone turnover. Thus, we measured bone formation and resorption markers before (study A) and after (study B) elimination of the morning peak of cortisol. We also assessed effects of the circadian cortisol pattern on serum calcium, PTH, and urinary calcium excretion. Ten normal postmenopausal women, aged 63-75 yr (mean, 69 yr), were studied. Metyrapone was administered to block endogenous cortisol synthesis and either a variable (study A) or a constant (study B) infusion of cortisol was given to reproduce and then abolish the morning cortisol peak. Blood was sampled every 2 h for serum cortisol, ionized calcium, PTH, and bone formation markers [osteocalcin and carboxyl-terminal propeptide of type I collagen (PICP)], and timed 4-h urine samples were collected for measurement of calcium, phosphorus, sodium, potassium, and bone resorption markers (N-telopeptide of type I collagen and free deoxypyridinoline). During study A, serum osteocalcin had a circadian pattern, with a peak at 0400 h and a nadir at 1400 h. During study B, however, the afternoon nadir of serum osteocalcin was eliminated (P < 0.001 and P < 0.005 for the difference in the patterns of peak and nadir, respectively, on the 2 study days). In contrast, the circadian patterns of serum PICP and urinary N-telopeptide of type I collagen and free deoxypyridinoline were virtually identical during the two studies. Urinary calcium excretion declined after the cortisol peak, without differences between the 2 study days in phosphorus or sodium excretion or in serum PTH. We conclude that the circadian variation in serum cortisol is responsible for the circadian pattern of serum osteocalcin, but not that of PICP or bone resorption markers. The physiological variation in serum cortisol may also reduce urinary calcium excretion.


The Relationship between Palatal Displacement of Upper Canines and Incisors Widths in a Syrian Sample of Patients with Uncrowded Arches.
The aim of this study investigates mesiodistal crown size of the maxillary and mandibular incisors of patients with palatally impacted canines (PDC). Pretreatment dental casts of orthodontic patients with PDC of one or both maxillary canines (N: 33) were collected. This PDC sample was matched according to age and sex with pretreatment dental casts from unaffected orthodontic patients. For the PDC and matched control samples, maximum mesiodistal crown diameters were recorded for the four incisors on the right side only. The results showed that, on average, the mesiodistal crown diameters for the maxillary and mandibular incisors measured smaller in the PDC sample than in the control sample. These findings of statistically significant tooth-size reductions associated with PDC occurrence indicate a generalized pattern of reduced tooth size as a characteristic associated with the PDC anomaly. Further, the presence of generalized tooth-size reduction in cases with palatally displaced canines help explain why most orthodontic treatment plans for PDC patients are of the nonextraction type.


Association Between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults With Cognitive Impairment.
Amyloid-β (Aβ) deposition is a feature of Alzheimer disease (AD) and may be promoted by exogenous factors, such as ambient air quality. To examine the association between the likelihood of amyloid positron emission tomography (PET) scan positivity and ambient air quality in individuals with cognitive impairment. This cross-sectional study used data from the Imaging Dementia-Evidence for Amyloid Scanning Study, which included more than 18 000 US participants with cognitive impairment who received an amyloid PET scan with 1 of 3 Aβ tracers (fluorine 18 [18F]-labeled florbetapir, 18F-labeled florbetaben, or 18F-labeled flutemetamol) between February 16, 2016, and January 10, 2018. A sample of older adults with mild cognitive impairment (MCI) or dementia was selected. Air pollution was estimated at the patient residence using predicted fine particulate matter (PM2.5) and ground-level ozone (O3) concentrations from the Environmental Protection Agency Downscaler model. Air quality was estimated at 2002 to 2003 (early, or approximately 14 [range, 13-15] years before amyloid PET scan) and 2015 to 2016 (late, or approximately 1 [range, 0-2] years before amyloid PET scan). Primary outcome measure was the association between air pollution and the likelihood of amyloid PET scan positivity, which was measured as odds ratios (ORs) and marginal effects, adjusting for demographic, lifestyle, and socioeconomic factors and medical comorbidities, including respiratory, cardiovascular, cerebrovascular, psychiatric, and neurological conditions. The data set included 18 178 patients, of which 10 991 (60.5%) had MCI and 7187 (39.5%) had dementia (mean [SD] age, 75.8 [6.3] years; 9333 women [51.3%]). Living in areas with higher estimated biennial PM2.5 concentrations in 2002 to 2003 was associated with a higher likelihood of amyloid PET scan positivity (adjusted OR, 1.10; 95% CI, 1.05-1.15; z score = 3.93; false discovery rate [FDR]-corrected P < .001; per 4-μg/m3 increments). Results were similar for 2015 to 2016 data (OR, 1.15; 95% CI, 1.05-1.26, z score = 3.14; FDR-corrected P = .003). An average marginal effect (AME) of +0.5% (SE = 0.1%; z score, 3.93; 95% CI, 0.3%-0.7%; FDR-corrected P < .001) probability of amyloid PET scan positivity for each 1-μg/m3 increase in PM2.5 was observed for 2002 to 2003, whereas an AME of +0.8% (SE = 0.2%; z score = 3.15; 95% CI, 0.3%-1.2%; FDR-corrected P = .002) probability was observed for 2015 to 2016. Post hoc analyses showed no effect modification by sex (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.04; z score = 1.13; FDR-corrected P = .56]; 2015-2016: β = 1.02 [95% CI, 0.98-1.07; z score = 0.91; FDR-corrected P = .56]) or clinical stage (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.03; z score = 0.77; FDR-corrected P = .58]; 2015-2016: β = 1.03; 95% CI, 0.99-1.08; z score = 1.46; FDR-corrected P = .47]). Exposure to higher O3 concentrations was not associated with amyloid PET scan positivity in both time windows. This study found that higher PM2.5 concentrations appeared to be associated with brain Aβ plaques. These findings suggest the need to consider airborne toxic pollutants associated with Aβ pathology in public health policy decisions and to inform individual lifetime risk of developing AD and dementia.


First results from the large probe infrared radiometer experiment.
During the descent to the surface of Venus, the large probe infrared radiometer measured the net thermal radiative flux in several spectral bandpasses. Preliminary analysis has permitted us to estimate (i) the infrared extinction coefficient profile attributable to aerosols, with respect to their visible profile, in the upper atmosphere of Venus and (ii) the water vapor mixing ratio below the clouds. An indication of the composition of a multicomponent cloud is seen in the data from the spectral bandpass from 6 to 7 micrometers.


[Dispensing of oral anticancer drugs by retail pharmacies: professional requirements and recommendations].
Objectives: As a result of organizational and therapeutic progress in the management of cancer, retail pharmacies are faced with numerous challenges in the follow-up of cancer patients. This study was designed to provide a better understanding of the way in which retail pharmacists define their role in the management of cancer patients and to identify actions that would promote more efficient coordination with other oncology professionals.Methods: Semi-structured qualitative interviews were conducted with retail pharmacists and data were analysed by thematic analysis.Results: The majority (53%) of retail pharmacists provide patients with explanations concerning their treatments. Participants in this study described in detail patients' questions concerning adverse effects (79%) as well as certain forms of alternative medicine (37%). Difficulties with an impact on patient follow-up were also reported, such as the lack of medical information concerning cancer treatments (21%) and their relationship with the hospital (26%).Conclusion: The availability of information tools shared by all healthcare professionals therefore appears to be essential to address the difficulties of follow-up of cancer patients by retail pharmacists.


Saturation and base composition bias explain phylogenomic conflict in Plasmodium.
Despite recent genome-based advances in understanding Plasmodium molecular evolution and its relationship to disease mechanisms and potential drug development, the phylogenetics of the group is currently limited to single-gene analyses. Here we develop and analyze a set of N100 putative orthologous genes derived from genome comparisons. We aimed to minimize systematic errors that arise when reconstructing the Plasmodium phylogeny with a genome-scale data set by evaluating the congruence of different genes, optimality criteria, and models of sequence evolution with previous studies encompassing fewer characters and more species. Saturation in substitutions and bias in base frequencies at third-codon positions characterized most Plasmodium genes. Molecular evolution models that partitioned rates of change by codon position were best at accounting for these sequence characteristics, as were analyses of amino acid alignments. These methods also ameliorated, but did not entirely avoid, the impact of reduced taxon sampling on phylogeny. The use of these models and expanded taxon sampling are necessary to maximize detection of multiple substitutions, overcome compositional biases, and, ultimately, resolve with confidence the phylogeny of Plasmodium.


Progressive alcohol-related liver fibrosis is characterised by imbalanced collagen formation and degradation.
Liver fibrosis accumulation is considered a turnover disease, with formation exceeding degradation, although this hypothesis has never been tested in humans. To investigate extracellular matrix (ECM) remodelling in a biopsy-controlled study of alcohol-related liver disease (ALD) patients. We evaluated the relationship between formation and degradation of four collagens as a function of histological fibrosis, inflammation and steatosis in 281 patients with ALD and 50 matched healthy controls. Post hoc, we tested the findings in a cohort of patients with alcohol-related cirrhosis and assessed the collagens' prognostic accuracy. We assessed the fibrillar collagens type III (PRO-C3/C3M) and V (PRO-C5/C5M), the basement membrane collagen IV (PRO-C4/C4M), and the microfilament interface collagen VI (PRO-C6/C6M). Mean age was 54 ± 6 years, 74% male, fibrosis stage F0/1/2/3/4 = 33/98/84/18/48. Compared to controls, patients with ALD had higher levels of type III collagen formation and degradation, with the highest concentrations in those with cirrhosis (PRO-C3 = 8.2 ± 1.7 ng/mL in controls, 14.6 ± 13.5 in ALD, 34.8 ± 23.1 in cirrhosis; C3M 7.4 ± 1.9 in controls, 9.3 ± 4.4 in ALD, 14.0 ± 5 in cirrhosis). ECM remodelling became increasingly imbalanced in higher stages of liver fibrosis, with formation progressively superseding degradation. This was particularly pronounced for type III collagen. We observed similar imbalance for inflammatory severity, but not steatosis. ALD is characterised by both elevated collagen formation and degradation, which becomes increasingly imbalanced with more severe disease. Net increase in fibrillar collagens contributes to fibrosis progression. This has important implications for monitoring and very early identification of patients at highest risk of progressing to cirrhosis.