Effectiveness of interventions to improve lifestyle behaviors among socially disadvantaged children in Europe.
Unhealthy lifestyle behaviors and childhood overweight are more common among children from families with a low socioeconomic position and ethnic minority children (referred to as social disadvantaged children). : This systematic review evaluates the effectiveness of interventions aimed to improve lifestyle behaviours and/or prevent overweight among socially disadvantaged children in Europe. : Six major databases were searched for studies reporting intervention effects on adiposity measures, sedentary behaviours, physical activity behaviours or dietary behaviours. Studies were included when the study sample consisted of at least 50% socially disadvantaged children or when results were presented for subgroups of socially disadvantaged children separately. Methodological quality assessment was based on Cochrane criteria. In total, 11 studies reporting on eight interventions (one among infants 0-2 years, one among preschoolers 2-6 years, six among school-aged children 6-12 years) were identified. Of these eight interventions, five interventions primarily aimed to improve at least one adiposity measure and three primarily aimed to improve a specific lifestyle behaviour. In general, modest positive effects were found but interventions were limited by a short follow-up duration. Despite an urgent need for effective interventions to improve lifestyle behaviours and prevent overweight among socially disadvantaged children, research on the effectiveness of interventions in Europe is still scarce. Those interventions that have been evaluated show modest effects on lifestyle behaviours and adiposity measures, but long-term follow-up is needed to establish whether these effects are sustained over a longer period of time.


Sunflower (Helianthus annuus) long-chain acyl-coenzyme A synthetases expressed at high levels in developing seeds.
Long chain fatty acid synthetases (LACSs) activate the fatty acid chains produced by plastidial de novo biosynthesis to generate acyl-CoA derivatives, important intermediates in lipid metabolism. Oilseeds, like sunflower, accumulate high levels of triacylglycerols (TAGs) in their seeds to nourish the embryo during germination. This requires that sunflower seed endosperm supports very active glycerolipid synthesis during development. Sunflower seed plastids produce large amounts of fatty acids, which must be activated through the action of LACSs, in order to be incorporated into TAGs. We cloned two different LACS genes from developing sunflower endosperm, HaLACS1 and HaLACS2, which displayed sequence homology with Arabidopsis LACS9 and LACS8 genes, respectively. These genes were expressed at high levels in developing seeds and exhibited distinct subcellular distributions. We generated constructs in which these proteins were fused to green fluorescent protein and performed transient expression experiments in tobacco cells. The HaLACS1 protein associated with the external envelope of tobacco chloroplasts, whereas HaLACS2 was strongly bound to the endoplasmic reticulum. Finally, both proteins were overexpressed in Escherichia coli and recovered as active enzymes in the bacterial membranes. Both enzymes displayed similar substrate specificities, with a very high preference for oleic acid and weaker activity toward stearic acid. On the basis of our findings, we discuss the role of these enzymes in sunflower oil synthesis.


Determination of the Structures of Uranyl-Tri-n-butyl-Phosphate Aggregates by Coupling Experimental Results with Molecular Dynamic Simulations.
The complex structure of a plutonium uranium refining by extraction (PUREX) process organic phase was characterized by combining results from experiments and molecular dynamics simulations. For the first time, the molecular interactions between tri-n-butyl phosphate (TBP) and the extracted solutes, as well as TBP aggregation after the extraction of water and/or uranyl nitrate, were described and analyzed concomitantly. Coupling molecular dynamics simulations with small- and wide-angle X-ray scattering (SWAXS) experiments can lead to simulated organic solutions that are representative of the experimental ones, even for high extractant and solute concentrations. Furthermore, this coupling is well adapted for the interpretation of SWAXS experiments without preliminary hypothesis on the size or shape of aggregates. The results link together previous literature studies obtained for each level of depiction separately (complexation or aggregation). Without uranium, or at low metal concentration, almost no aggregation was observed. At high uranium concentration, organic phases contain small [UO2 (NO3 )2 (TBP)2 ]n polymetallic aggregates (with n=2 to 4), in which the 1:2 U/TBP stoichiometry is preserved.


MNB/DYRK1A as a multiple regulator of neuronal development.
MNB/DYRK1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family that has been strongly conserved across evolution. There are substantial data implicating MNB/DYRK1A in brain development and adult brain function, as well as in neurodegeneration and Down syndrome pathologies. Here we review our current understanding of the neurodevelopmental activity of MNB/DYRK1A. We discuss how MNB/DYRK1A fulfils several sequential roles in neuronal development and the molecular mechanisms possibly underlying these functions. We also summarize the evidence behind the hypotheses to explain how the imbalance in MNB/DYRK1A gene dosage might be implicated in the neurodevelopmental alterations associated with Down syndrome. Finally, we highlight some research directions that may help to clarify the mechanisms and functions of MNB/DYRK1A signalling in the developing brain.


Composition and primary structure of the F1F0 ATP synthase from the obligately anaerobic bacterium Clostridium thermoaceticum.
The subunit composition and primary structure of the proton-translocating F1F0 ATP synthase have been determined in Clostridium thermoaceticum. The isolated enzyme has a subunit composition identical to that of the F1F0 ATP synthase purified from Clostridium thermoautotrophicum (A. Das, D. M. Ivey, and L. G. Ljungdahl, J. Bacteriol. 179:1714-1720, 1997), both having six different polypeptides. The molecular masses of the six subunits were 60, 50, 32, 17, 19, and 8 kDa, and they were identified as alpha, beta, gamma, delta, epsilon, and c, respectively, based on their reactivity with antibodies against the F1 ATPase purified from C. thermoautotrophicum and by comparing their N-terminal amino acid sequences with that deduced from the cloned genes of the C. thermoaceticum atp operon. The subunits a and b found in many bacterial ATP synthases could not be detected either in the purified ATP synthase or crude membranes of C. thermoaceticum. The C. thermoaceticum atp operon contained nine genes arranged in the order atpI (i), atpB (a), atpE (c), atpF (b), atpH (delta), atpA (alpha), atpG (gamma), atpD (beta), and atpC (epsilon). The deduced protein sequences of the C. thermoaceticum ATP synthase subunits were comparable with those of the corresponding subunits from Escherichia coli, thermophilic Bacillus strain PS3, Rhodospirillum rubrum, spinach chloroplasts, and the cyanobacterium Synechococcus strain PCC 6716. The analysis of total RNA by Northern hybridization experiments reveals the presence of transcripts (mRNA) of the genes i, a, and b subunits not found in the isolated enzyme. Analysis of the nucleotide sequence of the atp genes reveals overlap of the structural genes for the i and a subunits and the presence of secondary structures (in the b gene) which could influence the posttranscriptional regulation of the corresponding genes.


Breaking-bud pollination: a new pollination process in partially opened flowers by small bees.
Plant-pollinator interactions have usually been researched in flowers that have fully opened. However, some pollinators can visit flowers before full opening and contribute to fruit and seed sets. In this paper, we researched the pollination biology of flowers just starting to open in four field experiments. We observed the insect visitors to Lycoris sanguinea var. sanguinea for 3 years at five sites. These observations revealed that only small bees, Lasioglossum japonicum, often entered through tiny spaces between the tepals of 'breaking buds' (i.e. partially opened flowers) and collected pollen. We hypothesized that they can pollinate this species at the breaking-bud stage, when the stigma is located near the anthers. To measure the pollination effect of small bees at the breaking-bud stage, we bagged several breaking buds after small bees had visited them and examined whether these buds were pollinated. In bagging experiments, 30% of the breaking buds set fruit and seeds. Fruit-set ratios of the breaking buds did not differ significantly from those of the fully opened flowers, which had been visited by several insect species. We also counted the pollen grain numbers on the body of L. japonicum and on the anthers of randomly-selected and manipulated flowers. These experiments revealed that all of the captured bees had some pollen of target plants and that L. japonicum collected most of the pollen grains at the breaking-bud stage. Our results showed that the new pollination process, breaking-bud pollination, happened in breaking buds by L. japonicum, although there is no evidence to reveal that this is the most effective pollination method for L. sanguinea var. sanguinea. In principle, this new pollination process can occur in other flowering plants and our results are a major contribution to studies of plant-pollinator interactions.


[External cephalic version of breech presentation at term].
External cephalic version could be an alternative to either vaginal delivery or caesarean section in breech presentation at term. A systematic literature review about external cephalic version in breech presentation. The numbers of breech presentation delivered by caesarean section could probably be reduced in Norway by offering version, but this would not affect perinatal mortality.


Halorhabdus amylolytica sp. nov. and Halorhabdus salina sp. nov., isolated from hypersaline environments.
Two novel extremely halophilic archaeal strains, designated H27T and FL145T, were isolated from a salt mine and a kelp salt sample, respectively. Cells of both strains were Gram-stain-negative, motile and pleomorphic. The 16S rRNA and rpoB' gene sequence similarities between strains H27T and FL145T were 96.60 and 88.77%. Strains H27T and FL145T were both closely related to Halorhabdus rudnickae WSM-64T, Halorhabdus tiamatea SARL4BT and Halorhabdus utahensis AX-2T, with a 16S rRNA gene sequence similarities of 98.14, 96.34 and 96.27% for strain H27T and 96.42, 95.82 and 96.17% for strain FL145T. The genome-based average nucleotide identity (ANI) values between strains H27T and FL145T, and these three species were 83.93, 79.79 and 79.09% (for strain H27T), and 78.32, 77.95 and 77.05% (for strain FL145T), respectively. The ANI value between strains H27T and FL145T was 78.65 %. The digital DNA-DNA hybridization values between strains H27T and FL145T, and these three species were less than 27.40%, which were below the recommended threshold for membership of the same species. The major polar lipids of both strains were found to consist of sulfated diglycosyl diether, triglycosyl diether, phosphatidylglycerol phosphate methyl ester and phosphatidylglycerol. The DNA G+C content was determined from genome to be 62.10 mol% for strain H27T and 61.51 mol% for strain FL145T. Based on phylogenetic, phenotypic, chemotaxonomic and genomic analyses, these two new isolates should be classified as representing two novel species in the genus Halorhabdus, with strain H27T (=CGMCC 1.16342T=NBRC 113589T) as the type strain of a new species for which we propose the name Halorhabdus amylolytica sp. nov., and strain FL145T (=CGMCC 1.13888T=NBRC 114260T) as the type strain of another new species for which we propose the name Halorhabdus salina sp. nov.


Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation.
MicroRNAs have been explored in different organisms and are involved as molecular switches modulating cellular specification and differentiation during the embryonic development, including the cardiovascular system. In this study, we analyze the expression profiles of different microRNAs during early cardiac development. By using whole mount in situ hybridization in developing chick embryos, with microRNA-specific LNA probes, we carried out a detailed study of miR-23b, miR-130a, miR-106a, and miR-100 expression during early stages of embryogenesis (HH3 to HH17). We also correlated those findings with putative microRNA target genes by means of mirWalk and TargetScan analyses. Our results demonstrate a dynamic expression pattern in cardiac precursor cells from the primitive streak to the cardiac looping stages for miR-23b, miR-130a, and miR-106a. Additionally, miR-100 is later detectable during cardiac looping stages (HH15-17). Interestingly, the sinus venosus/inflow tract was shown to be the most representative cardiac area for the convergent expression of the four microRNAs. Through in silico analysis we revealed that distinct Hox family members are predicted to be targeted by the above microRNAs. We also identified expression of several Hox genes in the sinus venosus at stages HH11 and HH15. In addition, by means of gain-of-function experiments both in cardiomyoblasts and sinus venosus explants, we demonstrated the modulation of the different Hox clusters, Hoxa, Hoxb, Hoxc, and Hoxd genes, by these microRNAs. Furthermore, we correlated the negative modulation of several Hox genes, such as Hoxa3, Hoxa4, Hoxa5, Hoxc6, or Hoxd4. Finally, we demonstrated through a dual luciferase assay that Hoxa1 is targeted by miR-130a and Hoxa4 is targeted by both miR-23b and miR-106a, supporting a possible role of these microRNAs in Hox gene modulation during differentiation and compartmentalization of the posterior structures of the developing venous pole of the heart.


Innate immunity mediated by MyD88 signal is not essential for induction of lipopolysaccharide-specific B cell responses but is indispensable for protection against Salmonella enterica serovar Typhimurium infection.
Salmonella organisms are Gram negative and facultative anaerobic bacteria that cause typhoid fever in humans. In this study, we evaluated LPS-specific adaptive immunity in innate immune-deficient mice after oral administration of attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) strains. Of interest, identical levels of LPS-specific IgG and IgA Abs were elicited in the systemic (i.e., serum and spleen) and mucosal (i.e., fecal extract and small intestine) compartments of wild-type, TLR4(-/-), and MyD88(-/-) mice following oral vaccination with recombinant attenuated S. Typhimurium (RASV). Depletion of CD4(+) T cells during RASV vaccination completely abrogated the generation of LPS-specific Abs in MyD88(-/-) mice. In addition, mRNA expression levels of a B cell-activating factor of the TNF family were significantly increased in the spleens of MyD88(-/-) mice after oral administration, implying that T cell-independent B cell switching might be also enhanced in the MyD88 signal-deficient condition. Of most interest, orally vaccinated MyD88(-/-) mice that possessed high levels of LPS-specific IgG and IgA, which had a neutralizing effect against Salmonella, died earlier than nonvaccinated wild-type mice following lethal oral challenge with virulent Salmonella species. These results suggest that innate immunity mediated by MyD88 signal is dispensable for induction of LPS-specific Ab responses following oral administration of attenuated Salmonella strains but indispensable for efficient protection.


Trauma memories on trial: is cross-examination a safeguard against distorted analogue traumatic memories?
Trauma memories can feel more disorganised than more mundane memories. That may be problematic in legal contexts. Here we examined: (a) whether that disorganised feeling makes people more susceptible to suggestive questioning during direct examination; and (b) whether cross-examination is the safeguard it is purported to be: that is, we examined whether cross-examination can uncover and correct distorted trauma memories. We showed participants a film depicting a graphic car accident. For some participants, the film unfolded in a temporally disorganised way. We then interviewed participants immediately after the film regarding what they had seen: this 'direct examination' included free recall, cued recall and yes/no questions, some of which were misleading. Then, 48 hours later, a second interviewer cross-examined participants. Contrary to our predictions, neither manipulation of the film's temporal organisation, nor participants' self-reported feelings of event disorganisation significantly affected their accuracy of the film during direct or cross-examination nor their recognition memory of the film. Instead, we found that regardless of whether participants' memories were distorted by the direct examination, the suggestive nature of the cross-examination introduced sufficient doubt that participants were willing to change their answers. We conclude that traumatic memories are vulnerable to suggestive questioning and, unfortunately, cross-examination is not the legal system's fail-safe corrective influence.


Does Growth in the Executive System of Working Memory Underlie Growth in Literacy for Bilingual Children With and Without Reading Disabilities?
This cohort-sequential study explored the components of working memory (WM) that underlie second language (L2) reading growth in 450 children at risk and not at risk for reading disabilities (RD) whose first language is Spanish. English language learners designated as balanced and nonbalanced bilinguals with and without risk for RD in Grades 1, 2, and 3 at Wave 1 were administered a battery of cognitive (short-term memory, WM, naming speed, and inhibition), vocabulary, and reading measures in Spanish and English. These same measures were administered 1 and 2 years later. Two important findings occurred: First, growth in the WM executive component was significantly related to growth in English word identification and passage comprehension when competing measures (phonological processing, naming speed, inhibition, and fluid intelligence) were entered into the multilevel growth model. Second, children defined as at risk for RD in Wave 1 had lower intercepts than children not at risk at Wave 3 across several measures of cognition, language, and achievement. However, except on measures of the executive component of WM, no significant group differences in linear growth emerged. These findings suggest that growth in L2 reading was tied to growth in the executive system of WM.


[Formation and occurrence of cancer-producing hydrocarbons in cereals and possibilities for their reduction].
According to the authors' investigations every inhabitant of the GDR takes between 0.2 and 1.0 mg BaP. per year by food consumption including amounts of 0.03 to 0.17 mg on account of cereals and mill products. For the contamination of cereals the following sources are in consideration: environmental contamination on account of industry dust (distant from industry 0.1 to 0.6, near to industry 0.3 to 4.2 micrograms BaP/kg), passing over from soil to plant (with model experiments with soils more than 10 000 micrograms BaP/kg up to 22.3 micrograms BaP/kg dry matter) as well as technologically caused contamination for instance by direct fume-and-gas drying (with the use of raw lignite up to 10 micrograms BaP/kg). As it can be concluded from model experiments BaP passes to flour at milling in dependence of the extraction rate. By separating the husks prior to milling more than 50% of BaP can be removed from the stock.


Factors associated with psychotropic drug use among community-dwelling older persons: A review of empirical studies.
BACKGROUND: In the many descriptive studies on prescribed psychotropic drug use by community-dwelling older persons, several sociodemographic and other factors associated with drug use receive inconsistent support. METHOD: Empirical reports with data on at least benzodiazepine or antidepressant drug use in samples of older persons published between 1990 and 2001 (n = 32) were identified from major databases and analyzed to determine which factors are most frequently associated with psychotropic drug use in multivariate analyses. Methodological aspects were also examined. RESULTS: Most reports used probability samples of users and non-users and employed cross-sectional designs. Among variables considered in 5 or more reports, race, proximity to health centers, medical consultations, sleep complaints, and health perception were virtually always associated to drug use. Gender, mental health, and physical health status were associated in about two-thirds of reports. Associations with age, marital status, medication coverage, socioeconomic status, and social support were usually not observed. CONCLUSIONS: The large variety of methods to operationalize drug use, mental health status, and social support probably affected the magnitude of observed relationships. Employing longitudinal designs and distinguishing short-term from long-term use, focusing on samples of drug users exclusively, defining drug use and drug classes more uniformly, and utilizing measures of psychological well-being rather than only of distress, might clarify the nature of observed associations and the direction of causality. Few studies tested specific hypotheses. Most studies focused on individual characteristics of respondents, neglecting the potential contribution of health care professionals to the phenomenon of psychotropic drug use among seniors.


Extreme complications related to bevacizumab use in the treatment of ovarian cancer: a case series from a III level referral centre and review of the literature.
In patients undergoing debulking surgery for ovarian cancer (OC), bevacizumab-combined chemotherapy has been reported to be associated with an increased incidence of adverse events (AEs). Reports in the literature have noted the overall morbidity of bevacizumab to be between 3.7% and 9%. The aim of this study is to report uncommon and unusual manifestations of morbidity in surgical cases performed at our third level referral centers for gynecologic oncology. Additionally, we review the rare and severe bevacizumab-related complications that have been described in the literature. We defined as "extreme", the particularly rare and/or severe complications up to determining a life-threatening condition or death, which are related to the use of bevacizumab. A case-series of extreme complications registered at our institutions were reported. In addition, a literature search of the PubMed, MEDLINE and EMBASE electronic databases was performed for this review. The studies collected included: 8 randomized controlled trials (RCT) and 5 prospective observational, 1 prospective phase-IV, 10 prospective phase-II, 2 prospective phase-I, and 20 retrospective studies, as well as 9 case reports. Bevacizumab was administered as primary treatment in adjuvant and neo-adjuvant setting in 16 and 5 studies respectively, as treatment for recurrence in 36 trials, and for secondary cytoreductive surgery (SCS) in 3 studies. The overall population administered with bevacizumab numbered 7,096 women. Extreme complications were observed in 591 patients, with a morbidity rate of the 8.3%. Overall, central nervous system (CNS), cardiovascular, gastrointestinal (GI) and primary infectious complications were seen in 22 patients (0.3%), 261 patients (3.7%), 159 patients (2.2%), and 8 patients (0.13%), respectively. Hemorrhagic and wound complications occurred in 18 women (0.25%), and 112 women (1.6%), respectively. Extreme complications related to the use of bevacizumab are rare, and often go unrecognized. The recognition and immediate management of such rare and life-threatening complications in patients treated at third level referral centers could significantly improve patient survival.


Studies on laticiferous plants: toxic effects in goats of Calotropis procera latex given by different routes of administration.
The effects on goats of Calotropis procera latex given by different routes of administration were investigated. The administration of latex at 1 ml/Kg body weight via the oral route or at 0.005 ml/Kg body weight/day via the intravenous or intraperitoneal route caused death of the goats between 20 minutes and 4 days. When the small dose of latex (0.005 ml/Kg body weight/day) was given by the oral route or intramuscular route no death among the goats occurred. Nervous signs, frequent urination, frothing at the mouth, dyspnoea and diarrhoea were the main features in goats given latex by the oral, intravenous or intraperitoneal route. Lameness was observed in goats given latex via the intramuscular route. Lesions were widespread congestion and haemorrhage, pulmonary cyanosis, enterohepatonephropathy, peritonitis (in goats receiving latex via i.p. route) and haemorrhagic myositis at the site of latex injection. These changes were accompanied by increases in the activities of serum GDH, LDH, ALP, GGT and AST and in the concentrations of cholesterol, urea and creatinine and decreases in the level of total protein.


Musculoskeletal conditions in France.
Musculoskeletal conditions (MSC) are among the most frequent in adults in France, with over 20% of the population experiencing bone, joint, and muscle disorders. MSC are an increasing health concern in France, growing in importance on the public health agenda. Some of the present governmental plans are connected with MSC (Pain, the Disabled, Nutrition, Geriatrics). An overview of the present situation in France is provided, regarding the burden, the present situation, and steps forward. Scientific societies and patient groups are actively involved in campaigning in several fields; 2 examples are described: osteoporosis and rheumatoid arthritis and spondyloarthropathies. The Bone and Joint Decade initiative, officially endorsed by the French Government on June 20, 2000, provides the opportunity to develop more coordinated actions through the national network and international partnership as well (including the European League Against Rheumatism) to finally improve the health-related quality of life for people with MSC.


Deep Learning for Diagnosis of Chronic Myocardial Infarction on Nonenhanced Cardiac Cine MRI.
Background Renal impairment is common in patients with coronary artery disease and, if severe, late gadolinium enhancement (LGE) imaging for myocardial infarction (MI) evaluation cannot be performed. Purpose To develop a fully automatic framework for chronic MI delineation via deep learning on non-contrast material-enhanced cardiac cine MRI. Materials and Methods In this retrospective single-center study, a deep learning model was developed to extract motion features from the left ventricle and delineate MI regions on nonenhanced cardiac cine MRI collected between October 2015 and March 2017. Patients with chronic MI, as well as healthy control patients, had both nonenhanced cardiac cine (25 phases per cardiac cycle) and LGE MRI examinations. Eighty percent of MRI examinations were used for the training data set and 20% for the independent testing data set. Chronic MI regions on LGE MRI were defined as ground truth. Diagnostic performance was assessed by analysis of the area under the receiver operating characteristic curve (AUC). MI area and MI area percentage from nonenhanced cardiac cine and LGE MRI were compared by using the Pearson correlation, paired t test, and Bland-Altman analysis. Results Study participants included 212 patients with chronic MI (men, 171; age, 57.2 years ± 12.5) and 87 healthy control patients (men, 42; age, 43.3 years ± 15.5). Using the full cardiac cine MRI, the per-segment sensitivity and specificity for detecting chronic MI in the independent test set was 89.8% and 99.1%, respectively, with an AUC of 0.94. There were no differences between nonenhanced cardiac cine and LGE MRI analyses in number of MI segments (114 vs 127, respectively; P = .38), per-patient MI area (6.2 cm2 ± 2.8 vs 5.5 cm2 ± 2.3, respectively; P = .27; correlation coefficient, r = 0.88), and MI area percentage (21.5% ± 17.3 vs 18.5% ± 15.4; P = .17; correlation coefficient, r = 0.89). Conclusion The proposed deep learning framework on nonenhanced cardiac cine MRI enables the confirmation (presence), detection (position), and delineation (transmurality and size) of chronic myocardial infarction. However, future larger-scale multicenter studies are required for a full validation. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Leiner in this issue.


Mycobacterium tuberculosis infection causes different levels of apoptosis and necrosis in human macrophages and alveolar epithelial cells.
Mycobacterium tuberculosis interacts with macrophages and epithelial cells in the alveolar space of the lung, where it is able to invade and replicate in both cell types. M. tuberculosis-associated cytotoxicity to these cells has been well documented, but the mechanisms of host cell death are not well understood. We examined the induction of apoptosis and necrosis of human macrophages (U937) and type II alveolar epithelial cells (A549) by virulent (H37Rv) and attenuated (H37Ra) M. tuberculosis strains. Apoptosis was determined by both enzyme-linked immunosorbent assay (ELISA) and TdT-mediated dUTP nick end labelling (TUNEL) assay, whereas necrosis was evaluated by the release of lactate dehydrogenase (LDH). Both virulent and attenuated M. tuberculosis induced apoptosis in macrophages; however, the attenuated strain resulted in significantly more apoptosis than the virulent strain after 5 days of infection. In contrast, cytotoxicity of alveolar cells was the result of necrosis, but not apoptosis. Although infection with M. tuberculosis strains resulted in apoptosis of 14% of the cells on the monolayer, cell death associated with necrosis was observed in 59% of alveolar epithelial cells after 5 days of infection. Infection with M. tuberculosis suppressed apoptosis of alveolar epithelial cells induced by the kinase inhibitor, staurosporine. Because our findings suggest that M. tuberculosis can modulate the apoptotic response of macrophages and epithelial cells, we carried out an apoptosis pathway-specific cDNA microarray analysis of human macrophages and alveolar epithelial cells. Whereas the inhibitors of apoptosis, bcl-2 and Rb, were upregulated over 2.5-fold in infected (48 h) alveolar epithelial cells, the proapoptotic genes, bad and bax, were downregulated. The opposite was observed when U937 macrophages were infected with M. tuberculosis. Upon infection of alveolar epithelial cells with M. tuberculosis, the generation of apoptosis, as determined by the expression of caspase-1, caspase-3 and caspase-10, was inhibited. Inhibition of replication of intracellular bacteria resulted in an increase in apoptosis in both cell types. Our results showed that the differential induction of apoptosis between macrophages and alveolar epithelial cells represents specific strategies of M. tuberculosis for survival in the host.


Angiotensin II induces hyperresponsiveness of bronchial smooth muscle via an activation of p42/44 ERK in rats.
Angiotensin II (Ang II) might be an important mediator in the pathogenesis of bronchial asthma, although the mechanisms of airway hyperresponsiveness caused by Ang II are not yet clear. Whether p42/44 ERK contributes to the Ang II-elicited bronchial smooth muscle (BSM) hyperresponsiveness in rats was presently examined. The RT-PCR analyses revealed that Ang II AT(1A), AT(1B), and AT(2) receptors, angiotensinogen, angiotensin-converting enzyme, but not renin, were expressed in the lungs, trachea, and main bronchi of rats. Only a small and transient contraction was induced by the application of Ang II in the main bronchial smooth muscle; the contraction was inhibited by losartan, an AT(1) receptor antagonist. The contractions induced by carbachol (CCh), high K(+) depolarization, and sodium fluoride (NaF; a G protein activator) were augmented by pretreatment with Ang II. The BSM hyperresponsiveness induced by Ang II was abolished by losartan. Furthermore, the Ang II-induced BSM hyperresponsiveness to CCh was attenuated by pretreatment with U-0126, a p42/44 ERK kinase (MEK-1/2) inhibitor. In conclusion, Ang II-induced BSM hyperresponsiveness through the activation of p42/44 ERK may play an important role in the pathophysiology of bronchial asthma, although Ang II itself caused a small force development in the bronchial smooth muscle.


Transition dipole coupling in Amide I modes of betapolypeptides.
Our previous introduction of transition dipole coupling helped to explain the splittings in the Amide I modes of antiparallel chain pleated sheet polyglycine I. This mechanism has now been applied to the more likely rippled sheet structure of this polypeptide as well as to the pleated sheet structure of poly(L-alanine). A satisfactorily consistent explanation of the splittings in both polypeptides is obtained. Since a previously incorporated interaction constant has not been used in the present treatment, these results show that transition dipole coupling alone can provide the physical basis for understanding these splittings. It is therefore now possible to predict with confidence the hitherto unidentified v(pi,pi) frequency of the antiparallel chain pleated sheet as well as the characteristic frequencies of the parallel chain pleated sheet.


HDL cholesterol efflux normalised to apoA-I is associated with future development of type 2 diabetes: from the CORDIOPREV trial.
This prospective study evaluated whether baseline cholesterol efflux is associated with future development of type 2 diabetes (T2DM) in cardiovascular patients. We measured cholesterol efflux in all CORDIOPREV study (NCT00924937) participants free of T2DM at baseline (n = 462) and assessed its relationship with T2DM incidence during a 4.5 years of follow-up. Cholesterol efflux was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma. Disposition index was estimated as beta-cell function indicator. During follow-up 106 individuals progressed to T2DM. The cholesterol efflux/apoA-1 ratio was inversely associated with T2DM development independently of traditional risk factors (model-1, OR: 0.647, 95%CI: 0.495-0.846), and after additional adjustment for glycaemic parameters (model-2, OR: 0.670, 95%CI: 0.511-0.878). When cumulative incidence of diabetes was analysed by quartiles of cholesterol efflux/apoA-I, incidence of T2DM was reduced by 54% in subjects who were in the higher cholesterol efflux/apoA-I quartile compared to subjects in the lowest quartile (p = 0.018 and p = 0.042 for model-1 and 2). Moreover, participants who were in the higher cholesterol efflux/apoA-I presented significantly higher disposition index (β = 0.056, SE = 0.026; p = 0.035). In conclusion, HDL-cholesterol efflux normalised to apoA-I was inversely associated with T2DM development in cardiovascular patients. This association was independent of several T2DM risk factors, and may be related to a preserved beta-cell function.


Immunolocalization of keratan sulphate in the human embryonic cornea and other human foetal organs.
An antibody raised against keratan sulphate was used to localize keratan sulphate in the human embryonic cornea and other human foetal organs. It was found that keratan sulphate was present in the corneal endothelium, as well as in the corneal stroma. In contrast, no keratan sulphate could be demonstrated in the corneal epithelium or in any posterior parts of the human foetal eye. Human corneal stromal cells grown in monolayers in tissue culture lost their capacity to bind this antibody. This suggests that explantation in vitro decreases or alters the expression of keratan sulphate in this cell type. Keratan sulphate was found to be present in abundant quantities in human embryonic cartilage and to a lesser extent in placenta. In contrast, keratan sulphate could not be detected in the foetal intestine, liver, suprarenal glands, the umbilical cord or in the foetal yolk sack.


Hypermetabolic lesions of the pancreas on FDG PET/CT.
Interpretation of (18)F-FDG PET/CT studies in the pancreas is challenging owing to nonspecific FDG uptake in various benign and malignant pancreatic lesions. The purpose of this atlas article was to demonstrate features of various pancreatic lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging. We presented FDG PET/CT studies of 13 patients with various pancreatic lesions. All patients underwent abdominal enhanced CT before FDG PET/CT. We described these cases under the following categories: exocrine pancreatic cancer, cystic tumors, solid pseudopapillary tumor, neuroendocrine tumor, lymphoma, pancreatitis (focal acute and chronic pancreatitis, mass forming pancreatitis, and autoimmune pancreatitis), and infection. Knowledge of a wide spectrum of hypermetabolic pancreatic lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT.


Aftershocks and intensity of the managua earthquake of 23 december 1972.
Two portable seismic stations and a fixed array of five seismometers were used to record aftershocks in the vicinity of Managua, Nicaragua, after the earthquake of 23 December 1972. Approximately 3000 aftershocks were recorded during a 20-day period in January 1973. Left lateral motion along at least two faults, both trending N40 degrees E, is inferred from the seismic data. This is in good agreement with dislocations mapped at the surface in Managua. The data suggest that the shallow earthquakes of the Managua region are a consequence of north-south compressional stresses and east-west tensional stresses. This is consistent with regional plate movements deduced in other investigations.


Neighborhood Risk and Hospital Use for Pediatric Asthma, Rhode Island, 2005-2014.
Studies consistently show that children living in poor neighborhoods have worse asthma outcomes. The objective of our study was to assess the association between negative neighborhood factors (ie, neighborhood risk) and pediatric asthma hospital use. This retrospective study used data from children aged 2 to 17 years in a statewide (Rhode Island) hospital network administrative database linked to US Census Bureau data. We defined an asthma visit as an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code of 493 in any diagnosis field. We used 8 highly correlated measures for each census-block group to construct an index of neighborhood risk. We used maps and linear regression to assess the association of neighborhood risk with average annual census-block-group rates of asthma emergency department visits and hospitalizations. We used multivariable analyses to identify child characteristics and neighborhood risk associated with an asthma revisit, accounting for the child's sociodemographic information, season, and multiple measurements per child. From 2005 through 2014, we counted 359,195 visits for 146,889 children. Of these, 12,699 children (8.6%) had one or more asthma visits. Linear regression results showed 1.18 (95% confidence interval, 1.06-1.30) more average annual emergency departments visits per 100 children and 0.41 (95% confidence interval, 0.34-0.47) more average annual hospitalizations per 100 children in neighborhoods in the highest-risk index quintile than in neighborhoods in the lowest-risk index quintile. Interventions to improve asthma outcomes among children should move beyond primary care or clinic settings and involve a careful evaluation of social context and environmental triggers.


Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin.
UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL). A total of 9 healthy participants of skin types II to III were exposed to varying doses of artificial UV radiation without and after oral administration of PL (7.5 mg/kg). At 24 hours after exposure the erythema reaction was assessed and paired biopsy specimens were obtained from PL-treated and untreated skin. A significant decrease in erythema was found in PL-treated skin (P < .01). Histologically, PL-treated biopsy specimens showed less sunburn cells (P < .05), cyclobutane pyrimidine dimers (P < .001), proliferating epidermal cells (P < .001), and dermal mast cell infiltration (P < .05). A trend toward Langerhans cell preservation was seen. Oral administration of PL is an effective systemic chemophotoprotective agent leading to significant protection of skin against UV radiation.


Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor.
The highly aggressive character of melanoma makes it an excellent model for probing the mechanisms underlying metastasis, which remains one of the most difficult challenges in treating cancer. We find that miR-182, member of a miRNA cluster in a chromosomal locus (7q31-34) frequently amplified in melanoma, is commonly up-regulated in human melanoma cell lines and tissue samples; this up-regulation correlates with gene copy number in a subset of melanoma cell lines. Moreover, miR-182 ectopic expression stimulates migration of melanoma cells in vitro and their metastatic potential in vivo, whereas miR-182 down-regulation impedes invasion and triggers apoptosis. We further show that miR-182 over-expression promotes migration and survival by directly repressing microphthalmia-associated transcription factor-M and FOXO3, whereas enhanced expression of either microphthalmia-associated transcription factor-M or FOXO3 blocks miR-182's proinvasive effects. In human tissues, expression of miR-182 increases with progression from primary to metastatic melanoma and inversely correlates with FOXO3 and microphthalmia-associated transcription factor levels. Our data provide a mechanism for invasion and survival in melanoma that could prove applicable to metastasis of other cancers and suggest that miRNA silencing may be a worthwhile therapeutic strategy.


Data in support of energy performance of double-glazed windows.
This paper provides the data used in a research project to propose a new simplified windows rating system based on saved annual energy ("Developing an empirical predictive energy-rating model for windows by using Artificial Neural Network" (Shakouri Hassanabadi and Banihashemi Namini, 2012) [1], "Climatic, parametric and non-parametric analysis of energy performance of double-glazed windows in different climates" (Banihashemi et al., 2015) [2]). A full factorial simulation study was conducted to evaluate the performance of 26 different types of windows in a four-story residential building. In order to generalize the results, the selected windows were tested in four climates of cold, tropical, temperate, and hot and arid; and four different main orientations of North, West, South and East. The accompanied datasets include the annual saved cooling and heating energy in different climates and orientations by using the selected windows. Moreover, a complete dataset is provided that includes the specifications of 26 windows, climate data, month, and orientation of the window. This dataset can be used to make predictive models for energy efficiency assessment of double glazed windows.


Venovenous bypass in adult orthotopic liver transplantation: routine or selective use?
The role of venovenous bypass (VVB) during orthotopic liver transplantation (OLT) remains controversial. The aims of this study were to evaluate the current role of VVB at all major centers in North America, to examine the results of OLT and complications of VVB between two periods with a strict policy for routine versus selective use of VVB, and to review the literature. A survey of 50 major liver transplant centers was conducted using mailed questionnaires. A retrospective chart review was performed for 547 OLT patients having transplantation during two distinct periods with a strict policy for routine versus selective use of VVB at the University of Toronto, Canada, and at Duke University Medical Center, Durham, North Carolina. The literature was reviewed with a focus on the benefits and indications for routine versus selective use of VVB. Thirty-eight (76%) of 50 centers responded. Sixteen (42%) of them used VVB routinely, with a reported complication rate of 10-30%. Lymphocele and hematoma were the most common complications, but patients having major vascular injury, air embolism, and death were reported. A recent change to selective use of VVB was reported in 30% of the centers (11 of 38). In the Duke-Toronto series, the complication rates were similar between the two periods, at 13.4% and 18.8%, respectively. The outcome of OLT was not influenced by the policy of routine or selective use of VVB. There is a trend away from the routine use of VVB during OLT. Intraoperative hemodynamic instability during the hepatectomy and a failed trial of hepatic venous occlusion were the most important criteria for using VVB. We conclude that VVB should be used selectively to avoid associated complications and to decrease operative time and costs.


Surface characteristics of electrochemically oxidized implants and acid-etched implants: surface chemistry, morphology, pore configurations, oxide thickness, crystal structure, and roughness.
This study was undertaken to investigate surface properties of surface-modified titanium implants in terms of surface chemistry, morphology, pore characteristics, oxide thickness, crystal structure, and roughness. An oxidized, custom-made Mg implant, an oxidized commercially available implant (TiUnite), and a dual acid-etched surface (Osseotite) were investigated. Surface characteristics were evaluated with various surface analytic techniques. Surface chemistry showed similar fingerprints of titanium oxide and carbon contaminant in common for all implants but also revealed essential differences of the elements such as about 9 at% Mg for the Mg implant, about 11 at% P for the TiUnite implant and about 12 at% Na for the Osseotite implant. Surface morphology of the Mg and TiUnite implants demonstrated a duplex oxide structure, ie, an inner barrier layer without pores and an outer porous layer with numerous pores, whereas the Osseotite implant revealed a crystallographically etched appearance with pits. The diameter and depth of pores/pits was < or = 2 microm and < or = 1.5 microm in the Mg implant, < or = 4 microm and < or = 10 microm in the TiUnite implant, and < or = 2 microm and < or = 1 microm in the Osseotite implant, respectively. Oxide layer revealed homogeneous thickness, about 3.4 microm of all threads in the Mg implants. On the contrary, TiUnite showed heterogeneous oxide thickness, about 1 to 11 microm, which gradually increased with thread numbers. Crystal structure showed a mixture of anatase and rutile phase for the Mg implants. With respect to roughness, Sa showed 0.69 microm in the Mg implant, 1.35 microm in the TiUnite implant, and 0.72 microm in the Osseotite implant. Well-defined surface characterization may provide a scientific basis for a better understanding of the effects of the implant surface on the biological response. The surface-engineered implants resulted in various surface characteristics, as a result of different manufacturing techniques.


Killing of Streptococcus pneumoniae by capsular polysaccharide-specific polymeric IgA, complement, and phagocytes.
The role of IgA in the control of invasive mucosal pathogens such as Streptococcus pneumoniae is poorly understood. We demonstrate that human pneumococcal capsular polysaccharide-specific IgA initiated dose-dependent killing of S. pneumoniae with complement and phagocytes. The majority of specific IgA in serum was of the polymeric form (pIgA), and the efficiency of pIgA-initiated killing exceeded that of monomeric IgA-initiated killing. In the absence of complement, specific IgA induced minimal bacterial adherence, uptake, and killing. Killing of S. pneumoniae by resting phagocytes with immune IgA required complement, predominantly via the C2-independent alternative pathway, which requires factor B, but not calcium. Both S. pneumoniae-bound IgA and complement were involved, as demonstrated by a 50% decrease in killing with blocking of Fcalpha receptor (CD89) and CR1/CR3 (CD35/CD11b). However, IgA-mediated killing by phagocytes could be reproduced in the absence of opsonic complement by pre-activating phagocytes with the inflammatory products C5a and TNF-alpha. Thus, S. pneumoniae capsule-specific IgA may show distinct roles in effecting clearance of S. pneumoniae in the presence or absence of inflammation. These data suggest mechanisms whereby pIgA may serve to control pneumococcal infections locally and upon the pathogen's entry into the bloodstream.


Chirality parameter sensing based on surface plasmon resonance D-type photonic crystal fiber sensors.
We report a method to sense a surrounding chiral drug based on D-type single-mode photonic crystal fiber (PCF) sensors in this paper. The electromagnetic theory of surface plasmon resonance on metal-chiral drug structure is derived. The wave equation containing constitutive relations of a chiral drug is given and integrated into the finite element method to compute the effective refractive index, confinement loss, and plasmon resonance wavelength for a D-type PCF sensor immersed in the chiral drug. The effects of the chirality parameter on resonance behaviors are displayed. The wavelength sensitivities of the chirality parameter for the sensor changing with different kinds of metal film layers, side-polished depth, and thickness of metal film layer are calculated. The wavelength sensitivity can reach a maximum of 17,580 nm/chirality as the refractive index and chirality parameter of the drug are 1.36 and 0.08, respectively. Furthermore, simultaneous dual-parameter detection of the chirality parameter and refractive index is realized by using two different D-type PCF sensors with gold and silver metal film layers, respectively. This study may provide sufficient guidelines to the field of biochemical sensing.


Isolation of Klebsielleae from within living wood.
Previous studies from this laboratory have documented the presence of coliform bacteria emanating from wooden reservoirs containing finished drinking water. Coliforms were identified as Klebsiella pneumoniae and Enterobacter spp. In the present report, evidence is presented which suggests that the origin of these coliforms is from the wood used to construct the reservoirs. In liquid expressed from freshly cut redwood, total bacterial counts in the range of 10(5) to 10(6)/ml were commonly observed. When present, coliform counts were over 10(3)/ml of expressed liquid. E. agglomerans was the most prevalent coliform present, but Klebsiella was isolated from freshly cut logs. Citrobacter freundii was also occasionally isolated. No fecal coliform-positive Klebsiella were obtained from any of the samples. Highest total bacteria and coliform counts were observed in sapwood specimens. Coliforms were present throughout sapwood as evidenced by contact plating serial sections of freshly cut wood. Scanning electron micrographs illustrate the presence of bacterial colonies within sapwood tracheids. Other wood species also contained coliform bacteria but in numbers lower than found in redwood.


The HERBIVORE ELICITOR-REGULATED1 gene enhances abscisic acid levels and defenses against herbivores in Nicotiana attenuata plants.
Nicotiana attenuata plants can distinguish the damage caused by herbivore feeding from other types of damage by perceiving herbivore-associated elicitors, such as the fatty acid-amino acid conjugates (FACs) in oral secretions (OS) of Manduca sexta larvae, which are introduced into wounds during feeding. However, the transduction of FAC signals into downstream plant defense responses is still not well established. We identified a novel FAC-regulated protein in N. attenuata (NaHER1; for herbivore elicitor regulated) and show that it is an indispensable part of the OS signal transduction pathway. N. attenuata plants silenced in the expression of NaHER1 by RNA interference (irHER1) were unable to amplify their defenses beyond basal, wound-induced levels in response to OS elicitation. M. sexta larvae performed 2-fold better when reared on irHER1 plants, which released less volatile organic compounds (indirect defense) and had strongly reduced levels of several direct defense metabolites, including trypsin proteinase inhibitors, 17-hydroxygeranyllinallool diterpene glycosides, and caffeoylputrescine, after real and/or simulated herbivore attack. In parallel to impaired jasmonate signaling and metabolism, irHER1 plants were more drought sensitive and showed reduced levels of abscisic acid (ABA) in the leaves, suggesting that silencing of NaHER1 interfered with ABA metabolism. Because treatment of irHER1 plants with ABA results in both the accumulation of significantly more ABA catabolites and the complete restoration of normal wild-type levels of OS-induced defense metabolites, we conclude that NaHER1 acts as a natural suppressor of ABA catabolism after herbivore attack, which, in turn, activates the full defense profile and resistance against herbivores.


Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice.
We studied the effects of a neuraminidase inhibitor (oseltamivir) and an inhibitor of influenza virus polymerases (ribavirin) against two highly pathogenic H5N1 influenza viruses. In vitro, A/Vietnam/1203/04 virus (clade 1) was highly susceptible to oseltamivir carboxylate (50% inhibitory concentration [IC(50)] = 0.3 nM), whereas A/Turkey/15/06 virus (clade 2.2) had reduced susceptibility (IC(50) = 5.5 nM). In vivo, BALB/c mice were treated with oseltamivir (1, 10, 50, or 100 mg/kg of body weight/day), ribavirin (37.5, 55, or 75 mg/kg/day), or the combination of both drugs for 8 days, starting 4 h before virus inoculation. Monotherapy produced a dose-dependent antiviral effect against the two H5N1 viruses in vivo. Three-dimensional analysis of the drug-drug interactions revealed that oseltamivir and ribavirin interacted principally in an additive manner, with several exceptions of marginal synergy or marginal antagonism at some concentrations. The combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 1 mg/kg/day and the combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 10 mg/kg/day were synergistic against A/Vietnam/1203/04 and A/Turkey/15/06 viruses, respectively. These optimal oseltamivir-ribavirin combinations significantly inhibited virus replication in mouse organs, prevented the spread of H5N1 viruses beyond the respiratory tract, and abrogated the cytokine response (P < 0.01). Importantly, we observed clear differences between the efficacies of the drug combinations against two H5N1 viruses: higher doses were required for the protection of mice against A/Turkey/15/06 virus than for the protection of mice against A/Vietnam/1203/04 virus. Our preliminary results suggest that oseltamivir-ribavirin combinations can have a greater or lesser antiviral effect than monotherapy, depending on the H5N1 virus and the concentrations used.


Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences.
Males and females show distinct differences in action potential waveform, ion channel expression patterns, and ECG characteristics. However, it is not known how sex-based differences in Ca2+ cycling might contribute to these differences in electrophysiological activity. The goal of this study was to investigate the differences in cellular Ca2+ transients in males and females and to examine how these might contribute to electrophysiological function. Ca2+ transients were measured in individual myocytes within microscopic regions of the fluo-4 AM-loaded left ventricular epicardium of intact rat heart of both sexes (3 to 5 mo old). Pacing protocols were used to measure transient characteristics at a basic cycle length of 500 ms and during 10-s trains of rapid pacing delivered to the left ventricular apex. Ca2+ transients were smaller in magnitude and longer in duration in females than in males. More importantly, the variability in Ca2+ transient characteristics between myocytes in a microscopic recording site (heterogeneity index) was greater for females than males for characteristics related to transient duration. The rate sensitivity of Ca2+ alternans development in individual myocytes was greater in females than in males, but there was also a greater heterogeneity in cellular responses to the rate dependence of alternans development in females. The longer Ca2+ transients in females were also associated with slower restitution, which was likely to be responsible for the development of Ca2+ and repolarization alternans at slower heart rates. These results demonstrate that there are distinct differences in cellular Ca2+ cycling in male and female rat hearts. Not only is there slower reuptake of Ca2+ in female rats, but there is greater local variability in Ca2+ cycling at the microscopic level. These sex-based differences in Ca2+ cycling could contribute to differences in ECG morphology and in arrhythmia sensitivity in males and females.


Spatio-temporal properties of letter crowding.
Crowding between adjacent letters has been investigated primarily as a spatial effect. The purpose of this study was to investigate the spatio-temporal properties of letter crowding. Specifically, we examined the systematic changes in the degradation effects in letter identification performance when adjacent letters were presented with a temporal asynchrony, as a function of letter separation and between the fovea and the periphery. We measured proportion-correct performance for identifying the middle target letter in strings of three lowercase letters at the fovea and 10° in the inferior visual field, for a range of center-to-center letter separations and a range of stimulus onset asynchronies (SOA) between the target and flanking letters (positive SOAs: target preceded flankers). As expected, the accuracy for identifying the target letters reduces with decreases in letter separation. This crowding effect shows a strong dependency on SOAs, such that crowding is maximal between 0 and ∼100 ms (depending on conditions) and diminishes for larger SOAs (positive or negative). Maximal crowding does not require the target and flanking letters to physically coexist for the entire presentation duration. Most importantly, crowding can be minimized even for closely spaced letters if there is a large temporal asynchrony between the target and flankers. The reliance of letter identification performance on SOAs and how it changes with letter separations imply that the crowding effect can be traded between space and time. Our findings are consistent with the notion that crowding should be considered as a spatio-temporal, and not simply a spatial, effect.


Single nanomaterial level investigation of ZnO nanorod sulfidation reactions via position resolved confocal Raman spectroscopy.
Zinc oxide (ZnO) nanomaterials have been used as desulfurizing sorbents for gaseous streams, zinc sulfide (ZnS)-forming template lattices in nanomaterial synthesis, and agriculturally produced sulfur (S)-removing reagents from the environment. Although various nanoscale forms of ZnO have already been utilized widely for such purposes, there is currently a lack of fundamental insight into the sulfidation of ZnO nanomaterials at the single nanocrystal level. We demonstrate that position-resolved confocal Raman spectroscopy can be successfully used to reveal the sulfidation process of ZnO NRs occurring at the single nanomaterial level. We attained a single crystal level understanding of the facet-dependent sulfidation reactivity of ZnO NRs by tracking the same NRs with Raman spectroscopy before and after the sulfidation reaction and quantitatively analyzing various ZnS-induced phonon scattering intensities from different positions on the NRs. The trend in NR facet-dependent sulfidation reactivity is further substantiated by correlating it with the electron microscopy and fluorescence data measured from the same NRs. The insight obtained from this study may provide the much-needed fundamental knowledge base for designing optimal ZnO nanostructures beneficial to many technological and industrial applications exploiting the ZnO-to-ZnS conversion. Taken together with the well-established methods to synthesize ZnO nanomaterials of specific crystal shapes and structures, our findings from this study may be broadly applicable in formulating and optimizing more advanced, low-dimensional ZnO sorbents and scrubbers for highly effective S removal.


Body mass index and colorectal cancer risk: A Mendelian randomization study.
Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2 ) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.


Electromyographic mixed nerve and cutaneous silent period in evaluating the A-delta fibres in a patient with hereditary sensory-autonomic neuropathy.
The aim of this study was to evaluate A-delta fibre function in a patient with hereditary sensory-autonomic neuropathy (HSAN). We used the mixed and cutaneous silent period techniques in addition to a conventional electromyographic investigation in a patient with type 2 HSAN, a rare disease characterised by wide-spread sensory and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. Whereas the stimulation of one digital nerve did not show any evidence of silent period in either the left or the right hand, the simultaneous stimulation of two digital nerves, as well as the stimulation of a mixed nerve, revealed a measurable delayed and shortened silent period. These data suggest that a spatial summation mediated by A-delta fibres was required for generation of the silent period in this patient and that combining the CSP and MNSP may be of practical use in evaluating impairment of the small myelinated fibres.


Quantification of carbonate by gas chromatography-mass spectrometry.
Carbon dioxide and carbonates are widely distributed in nature, are constituents of inorganic and organic matter, and are essential in vegetable and animal organisms. CO(2) is the principal greenhouse gas in the atmosphere. In human blood, CO(2)/HCO(3)(-) is an important buffering system. Quantification of bicarbonate and carbonate in inorganic and organic matter and in biological fluids such as blood or blood plasma by means of the GC-MS technology has been impossible so far, presumably because of the lack of suitable derivatization reactions to produce volatile and thermally stable derivatives. Here, a novel derivatization reaction is described for carbonate that allows for its quantification in aqueous alkaline solutions and alkalinized plasma and urine. Carbonate in acetonic solutions of these matrices (1:4 v/v) and added (13)C-labeled carbonate for use as the internal standard were heated in the presence of the derivatization agent pentafluorobenzyl (PFB) bromide for 60 min and 50 °C. Investigations with (12)CO(3)(2-), (13)CO(3)(2-), (CH(3))(2)CO, and (CD(3))(2)CO in alkaline solutions and GC-MS and GC-MS/MS analyses under negative-ion chemical ionization (NICI) or electron ionization (EI) conditions of toluene extracts of the reactants revealed formation of two minor [i.e., PFB-OCOOH and O=CO(2)-(PFB)(2)] and two major [i.e., CH(3)COCH(2)-C(OH)(OPFB)(2) and CH(3)COCH=C(OPFB)(2)] carbonate derivatives. The latter have different retention times (7.9 and 7.5 min, respectively) but virtually identical EI and NICI mass spectra. It is assumed that CH(3)COCH(2)-C(OH)(OPFB)(2) is formed from the reaction of the carbonate dianion with two molecules of PFB bromide to form the diPFB ester of carbonic acid, which further reacts with one molecule of acetone. Subsequent loss of water finally generates the major derivative CH(3)COCH=C(OPFB)(2). This derivatization reaction was utilized to quantify total CO(2)/HCO(3)(-)/CO(3)(2-) (tCO(2)) in human plasma and urine by GC-MS in the NICI mode by selected ion monitoring of the anions [M-H](-) of CH(3)COCH=C(OPFB)(2) at m/z 461 for the endogenous species and m/z 462 for the internal standard (13)CO(3)(2-). Oral intake of the carboanhydrase inhibitor drug acetazolamide by two healthy volunteers resulted in temporary increased excretion of tCO(2) in the urine. The method is specific for carbonate, accurate, sensitive and should be applicable to various matrices including human fluids and environmental samples.


Smart orthopaedic implants: A targeted approach for continuous postoperative evaluation in the spine.
Real-time health monitoring systems are emerging in diverse medical fields, tracking biological and physiological signals for direct feedback to the user. Orthopaedics is yet to adapt to innovative trends in health monitoring. Despite an evident entry point during orthopaedic surgeries, clinicians remain unable to objectively examine the structural integrity and biomechanics in the operated region through implantable sensors. As such, postoperative advice can be non-specific and poorly guided. This perspective discusses the clinical need for load-sensing implants that address biomechanical postoperative monitoring, taking the example of spinal interbody cages. Research has attempted to establish sensing approaches in different orthopaedic settings; however, they fail to meet mechanical sensing requirements or lack in vivo translatability, especially in the spine. Polymeric flexible sensors and Microelectromechanical Systems (MEMS) have favourable attributes aligned to the required features for in vivo load-sensing, although these approaches are yet to be tested extensively in orthopaedics. While inductive powering is promising, wireless energy transfer and telemetry are areas of ongoing research. This perspective proposes a thorough understanding of the relevant biomechanics to identify the pertinent sensing parameters, concurrent treatment of sensing and powering aspects, and utilisation of energy harvesting for sensing and data transmission. While sensing advancements have contributed to the rise of real-time health monitoring in other fields of medicine, orthopaedics has so far been overlooked. It is the application of these innovations that will lead to the development of a new generation of 'smart' implants for continuous postoperative evaluation.


Cross-talk between GlcNAcylation and phosphorylation: site-specific phosphorylation dynamics in response to globally elevated O-GlcNAc.
Protein GlcNAcylation serves as a nutrient/stress sensor to modulate the functions of many nuclear and cytoplasmic proteins. O-GlcNAc cycles on serine or threonine residues like phosphorylation, is nearly as abundant, and functions, at least partially, via its interplay with phosphorylation. Here, we describe changes in site-specific phosphorylation dynamics in response to globally elevated GlcNAcylation. By combining sequential phospho-residue enrichment, iTRAQ labeling, and high throughput mass spectrometric analyses, phosphorylation dynamics on 711 phosphopeptides were quantified. Based upon their insensitivity to phosphatase inhibition, we conclude that approximately 48% of these phosphorylation sites were not actively cycling in the conditions of the study. However, increased GlcNAcylation influenced phosphate stoichiometry at most of the sites that did appear to be actively cycling. Elevated GlcNAcylation resulted in lower phosphorylation at 280 sites and caused increased phosphorylation at 148 sites. Thus, the cross-talk or interplay between these two abundant posttranslational modifications is extensive, and may arises both by steric competition for occupancy at the same or proximal sites and by each modification regulating the other's enzymatic machinery. The phosphoproteome dynamics presented by this large set of quantitative data not only delineates the complex interplay between phosphorylation and GlcNAcyation, but also provides insights for more focused investigations of specific roles of O-GlcNAc in regulating protein functions and signaling pathways.


Chloroplast tRNA gene contains a long intron in the D stem: Nucleotide sequences of tobacco chloroplast genes for tRNA (UCC) and tRNA (UCU).
The nucleotide sequences of tobacco chloroplast genes for tRNA(Gly) (UCC) and tRNA(Arg) (UCU) have been determined. The tRNA(Gly) gene has a 691-base-pair intron located in the D stem while the tRNA(Arg) gene does not have any intron. The tRNA(Gly) and tRNA(Arg) genes are encoded on the same strand and separated by a 169-base-pair spacer. The tRNA(Gly) gene is transcribed as a 900-base precursor RNA molecule. The tRNA(Gly) and tRNA(Arg) deduced from the DNA sequences show 84% and 55% sequence homologies with Escherichia coli tRNA(Gly) (UCC) and phage T4 tRNA(Arg) (UCU), respectively.


A unified model for the dynamics of ATP-independent ultrafast contraction.
In nature, several ciliated protists possess the remarkable ability to execute ultrafast motions using protein assemblies called myonemes, which contract in response to Ca2+ ions. Existing theories, such as actomyosin contractility and macroscopic biomechanical latches, do not adequately describe these systems, necessitating development of models to understand their mechanisms. In this study, we image and quantitatively analyze the contractile kinematics observed in two ciliated protists (Vorticella sp. and Spirostomum sp.), and, based on the mechanochemistry of these organisms, we propose a minimal mathematical model that reproduces our observations as well as those published previously. Analyzing the model reveals three distinct dynamic regimes, differentiated by the rate of chemical driving and the importance of inertia. We characterize their unique scaling behaviors and kinematic signatures. Besides providing insights into Ca2+-powered myoneme contraction in protists, our work may also inform the rational design of ultrafast bioengineered systems such as active synthetic cells.


Cognitive Training Does Not Enhance General Cognition.
Due to potential theoretical and societal implications, cognitive training has been one of the most influential topics in psychology and neuroscience. The assumption behind cognitive training is that one's general cognitive ability can be enhanced by practicing cognitive tasks or intellectually demanding activities. The hundreds of studies published so far have provided mixed findings and systematic reviews have reached inconsistent conclusions. To resolve these discrepancies, we carried out several meta-analytic reviews. The results are highly consistent across all the reviewed domains: minimal effect on domain-general cognitive skills. Crucially, the observed between-study variability is accounted for by design quality and statistical artefacts. The cognitive-training program of research has showed no appreciable benefits, and other more plausible practices to enhance cognitive performance should be pursued.


Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis.
The present study was planned to investigate the relationship between the plasma lipid profile and disease activity in patients with a first clinical episode suggestive of multiple sclerosis (MS). Eighteen consecutive out-patients underwent a monthly brain magnetic resonance imaging (MRI), blood sample and neurological assessment over 6 months. Blood samples were used to evaluate total cholesterol and triglyceride levels as well as their lipoprotein fractions. Plasma total apolipoprotein E concentration was also determined. We found a significant correlation between the mean number of enhancing lesions and the mean plasma level of both total and low density lipoprotein cholesterol. The total plasma cholesterol level increased on average by 4.4 mg/dl for each enhancing lesion. Our preliminary data suggest a potential role of plasma cholesterol level as a biological marker of disease activity after a first demyelinating event. Further studies need, however, to be designed to determine whether the plasma cholesterol level is of practical use in monitoring the disease course.


Assessment of the results of a three-year program for National Standardization and Quality Improvement of Medical Laboratories on Drug of Abuse Testing by the Ministry of Health in Turkey.
The aim of this study is to assess the results of inspections in the last three years of drug abuse testing in medical laboratories according to the latest regulations in Turkey. The on-site inspections of medical laboratories for drugs abuse testing performed in Alcohol and Drug Addiction Treatment Centers during 2014-2016 are described, and laboratory processes and performance evaluated. The performance of 35 laboratories in 2014, 62 laboratories in 2015, and 94 laboratories in 2016 were scored as the sum of the scores for all answers on the inspection form. An inspected laboratory was considered to have an unconformity if the total score was less than 2/3 of maximum score. The total scores of inspections and the number of laboratories with between years were compared using one-way analysis of variance and slope Chi-square for trend test, respectively. Total scores increased statistically significantly from 35.9 ± 16.2 in 2014, to 43.5 ± 16.3 in 2015 and 49.1 ± 1.3 in 2016 (p < 0.001). The laboratories with unconformities decreased statistically significantly from 57% in 2014 to 37% in 2015 and 22% in 2016 (p < 0.001). The published legislation and the inspections contributed to national standardization and improved quality of service in medical laboratories for drug abuse testing.


Long-term regeneration and remodeling of the pig esophagus after circumferential resection using a retrievable synthetic scaffold carrying autologous cells.
Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus. Current reconstruction approaches are limited to utilization of an autologous conduit such as stomach, small bowel, or colon. A tissue engineered construct providing an alternative for esophageal replacement in circumferential, full thickness resection would have significant clinical applications. In the current study, we demonstrate that regeneration of esophageal tissue is feasible and reproducible in a large animal model using synthetic polyurethane electro-spun grafts seeded with autologous adipose-derived mesenchymal stem cells (aMSCs) and a disposable bioreactor. The scaffolds were not incorporated into the regrown esophageal tissue and were retrieved endoscopically. Animals underwent adipose tissue biopsy to harvest and expand autologous aMSCs for seeding on electro-spun polyurethane conduits in a bioreactor. Anesthetized pigs underwent full thickness circumferential resection of the mid-lower thoracic esophagus followed by implantation of the cell seeded scaffold. Results from these animals showed gradual structural regrowth of endogenous esophageal tissue, including squamous esophageal mucosa, submucosa, and smooth muscle layers with blood vessel formation. Scaffolds carrying autologous adipose-derived mesenchymal stem cells may provide an alternative to the use of a gastro-intestinal conduit for some patients following resection of the esophagus.


[UPLC-Q-TOF-MS analysis of naringin and naringenin and its metabolites in rat plasma after intragastrical administration of alcohol extract of exocarpium Citri grandis].
To analyze naringin, naringenin and its metabolites in rat plasma after intragastric administration of exocarpium Citri grandis alcohol extract. Rat blood samples were collected 1.0 hour after oral administration of 50 g x kg(-1) exocarpium Citri grandis alcohol extract and analyzed by UPLC-Q-TOF with MS(E) function. The post-acquisition data were processed using Metabolynx. Naringin (M1), naringenin (M2), naringin-5-O-glucuronide (M3), naringin-4-O-glucuronide (M4), glucuronide conjugate of naringenin (M5), naringin-4-O-sulfate (M6), methylated conjugate of hydroxylated naringenin (M7), glucuronide and sulfate conjugate of naringenin (M8), glucuronide conjugate of hydroxylated naringenin (M9) in rat plasma were detected. M3, M4, M6 were first reported as the metabolites of naringin. M7, M9 were first reported as the metabolites of naringenin. The results indicated that naringin, naringenin can be metabolited as the forms of glucuronidation, sulfation and naringenin can also be metabolited as the forms of methylation with hydroxylation and glucuronidation with hydroxylation in vivo after administration.


A divergence between underlying and final causes of death in selected conditions: an analysis of death registries in Peru.
The underlying cause of death is used to study country and global mortality trends and profiles. The final cause of death could also inform the ultimately cause of death in individuals with underlying conditions. Whether there is a pattern between the underlying and final cause of death has not been explored using national death registries. We studied what final causes of death were most common among selected underlying causes using national death registries in Peru, 2015. Underlying and final causes of death were classified according to their ICD-10 codes. Underlying causes included chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), hypertension (HTN), diabetes, and selected cancers (cervix, breast, stomach, prostate, and lung). Final causes were categorized as: communicable, cardiovascular, and cancers. Descriptive statistics were used. A total of 77,065 death registries were analyzed; cases had a mean age of 69.4 (SD: 19.3) years at death and were mostly men (53.9%). When the underlying cause was HTN, the most frequent final cause was cardiovascular diseases (82.3%). For all the other underlying causes, the most frequent final cause was communicable diseases: COPD (86.4%), CKD (79.3%), cancer (76.5%), and diabetes (68.3%). In four selected underlying causes of death there was a divergence with respect to the final cause, suggesting there was a shift from non-communicable to communicable causes. Although efforts should be deployed to prevent underlying non-communicable diseases, potential communicable complications should not be neglected.


Gene and genome construction in yeast.
The yeast Saccharomyces cerevisiae has the capacity to take up and assemble dozens of different overlapping DNA molecules in one transformation event. These DNA molecules can be single-stranded oligonucleotides, to produce gene-sized fragments, or double-stranded DNA fragments, to produce molecules up to hundreds of kilobases in length, including complete bacterial genomes. This unit presents protocols for designing the DNA molecules to be assembled, transforming them into yeast, and confirming their assembly.


Muscle variants of the upper and lower limb (with anatomical correlation).
Several accessory muscles in the upper and lower limb have been described in the medical literature. Most are asymptomatic and represent incidental findings at imaging. In some instances, however, these muscles may become clinically relevant producing palpable swelling, entrapment of neurovascular structures, or exercise-related pain. The diagnosis of accessory muscles is based on recognition of their typical location and on cross-sectional imaging features. Familiarity with their most common location and knowledge of the possible clinical syndromes caused by these supernumerary structures may aid in diagnosis and treatment.


In the Wild HRI Scenario: Influence of Regulatory Focus Theory.
Research related to regulatory focus theory has shown that the way in which a message is conveyed can increase the effectiveness of the message. While different research fields have used this theory, in human-robot interaction (HRI), no real attention has been given to this theory. In this paper, we investigate it in an in the wild scenario. More specifically, we are interested in how individuals react when a robot suddenly appears at their office doors. Will they interact with it or will they ignore it? We report the results from our experimental study in which the robot approaches 42 individuals. Twenty-nine of them interacted with the robot, while the others either ignored it or avoided any interaction with it. The robot displayed two types of behavior (i.e., promotion or prevention). Our results show that individuals that interacted with a robot that matched their regulatory focus type interacted with it significantly longer than individuals that did not experience regulatory fit. Other qualitative results are also reported, together with some reactions from the participants.


[Analysis of macrophage functional activity during adhesion].
Using the phenomenon of the formation of the active forms of oxygen by phagocytes in the process of adhesion, changes occurring in the cell membrane under the influence of sodium caseinate, macrophage migration inhibition factor, aggregated IgG and hydrolytic enzymes could be registered. Sodium caseinate inhibited chemiluminescence during the first 10 minutes in the adhesion of mouse peritoneal macrophages, human lung macrophages and adhesive marrow cells, while large doses of this preparation activated chemiluminescence at the latter stages of adhesion. Macrophage migration inhibition factor induced the rapid and prolonged formation of the active forms of oxygen in the process of macrophage adhesion, aggregated IgG decreased this cell function, and the subsequent phagocytosis of zymosan was accompanied by increased chemiluminescence. The experimental and practical possibilities of this phenomenon are discussed.


[Oral dormicum premedication of children in day surgery].
Thirty-four patients aged 5-14 years were observed, divided into age groups OF 5-8 and 8-14 years. Cardiovascular function was evaluated by central hemodynamic parameters and cardiointervalography. Changes in external respiration parameters were studied. The efficacy of premedication was assessed by objective parameters and by clinical signs. Each patient was examined 4 times at the following stages: 1) before premedication; 2) at the 10th min; 3) at the 20th min; and 4) at the 30th min. Oral premedication with dormicum in a dose of 0.5 mg/kg did not affect heart rate or arterial pressure. By the 20th min it notably decreased total peripheral resistance, significantly decreased the respiratory volume, increased respiration rate, and decreased sympathetic tone in younger children. In older children the premedication virtually did not affect total peripheral resistance and facilitated heart work, increased the respiratory volume, rarefied the respiratory rate, and did not affect the autonomic regulation balance. Younger children fell asleep without excitation or negativism; 35.2% developed psychomotor reactions. In older group the effect was good in 71.1% children, the rest had "apparitions" starting from the 17th min: doubling of the staff's faces, white spiders, or white moths.


Gastrointestinal bleeding with severe mucosal involvement in a patient with generalized pustular psoriasis without IL36RN mutation.
Generalized pustular psoriasis (GPP) is a systemic inflammatory disease that presents with erythema and sterile pustules, pathologically characterized by Kogoj's spongiform pustules. GPP is sometimes accompanied by mucosal involvement, and the most common lesion is on the tongue. IL36RN mutation was found to contribute to the pathogenesis of GPP especially in patients who develop GPP without a past medical history of psoriasis vulgaris. The association of IL36RN mutation with mucosal involvement in GPP is controversial. We herein report a 60-year-old male GPP patient with no past history of plaque psoriasis presenting with not only severe skin lesions and arthritis but also severe mucosal involvements of pharyngeal and gastrointestinal lesions, which led to gastrointestinal bleeding. Our case did not have any mutation in the IL36RN gene. We should be aware that severe GPP can cause gastrointestinal bleeding. The relevancy of IL36RN mutation with mucosal involvement in GPP remains to be elucidated.


Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past.
Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus strain disease, has recently emerged in China and rapidly spread worldwide. This novel strain is highly transmittable and severe disease has been reported in up to 16% of hospitalized cases. More than 600,000 cases have been confirmed and the number of deaths is constantly increasing. COVID-19 hospitalized patients, especially those suffering from severe respiratory or systemic manifestations, fall under the spectrum of the acutely ill medical population, which is at increased venous thromboembolism risk. Thrombotic complications seem to emerge as an important issue in patients infected with COVID-19. Preliminary reports on COVID-19 patients' clinical and laboratory findings include thrombocytopenia, elevated D-dimer, prolonged prothrombin time, and disseminated intravascular coagulation. As the pandemic is spreading and the whole picture is yet unknown, we highlight the importance of coagulation disorders in COVID-19 infected patients and review relevant data of previous coronavirus epidemics caused by the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV).


Accurate Heart Rate and Respiration Rate Detection Based on a Higher-Order Harmonics Peak Selection Method Using Radar Non-Contact Sensors.
Vital signs such as heart rate and respiration rate are among the most important physiological signals for health monitoring and medical applications. Impulse radio (IR) ultra-wideband (UWB) radar becomes one of the essential sensors in non-contact vital signs detection. The heart pulse wave is easily corrupted by noise and respiration activity since the heartbeat signal has less power compared with the breathing signal and its harmonics. In this paper, a signal processing technique for a UWB radar system was developed to detect the heart rate and respiration rate. There are four main stages of signal processing: (1) clutter removal to reduce the static random noise from the environment; (2) independent component analysis (ICA) to do dimension reduction and remove noise; (3) using low-pass and high-pass filters to eliminate the out of band noise; (4) modified covariance method for spectrum estimation. Furthermore, higher harmonics of heart rate were used to estimate heart rate and minimize respiration interference. The experiments in this article contain different scenarios including bed angle, body position, as well as interference from the visitor near the bed and away from the bed. The results were compared with the ECG sensor and respiration belt. The average mean absolute error (MAE) of heart rate results is 1.32 for the proposed algorithm.


Knowledge, Attitudes, and Practices Regarding Menstrual Hygiene among Girls in Ghizer, Gilgit, Pakistan.
Menstrual hygiene is a critical issue encountered by women and girls of reproductive age that negatively affects their health and empowerment. It is still deemed a taboo subject in several parts of the world, and girls hesitate to discuss menstruation with their family members, friends, or schoolteachers, which creates hurdles when they experience their menarche. Girls residing in rural areas encounter more problems, since they lack proper resources and knowledge to manage their menstruation in school as well as at home. The purpose of this study was to evaluate the knowledge, attitudes, and practices regarding the menstrual hygiene of girls residing in rural areas of Gilgit, Pakistan. A descriptive cross-sectional design was used to assess the study questions. The consecutive sampling technique was applied to recruit 300 female participants from remote areas of Gilgit, Pakistan, who were 13 to 22 years old. A pre-tested questionnaire was utilized to collect the data, and SPSS version 21.0 was used to analyze them. The study found that more than half of the participants had a poor level of knowledge and practices and negative attitudes towards menstrual hygiene. This could be due to many cultural and social factors associated with menstrual hygiene. The study concluded that the study participants were not knowledgeable about menstrual hygiene. They had poor practices and attitudes regarding menstrual hygiene. Hence, it is recommended that frequent sessions should be conducted by healthcare workers to enhance the knowledge of parents, teachers, and young girls, to increase their positive attitudes and practices regarding menstrual hygiene.


AI in Rehabilitation Medicine: Opportunities and Challenges.
Artificial intelligence (AI) tools are increasingly able to learn from larger and more complex data, thus allowing clinicians and scientists to gain new insights from the information they collect about their patients every day. In rehabilitation medicine, AI can be used to find patterns in huge amounts of healthcare data. These patterns can then be leveraged at the individual level, to design personalized care strategies and interventions to optimize each patient's outcomes. However, building effective AI tools requires many careful considerations about how we collect and handle data, how we train the models, and how we interpret results. In this perspective, we discuss some of the current opportunities and challenges for AI in rehabilitation. We first review recent trends in AI for the screening, diagnosis, treatment, and continuous monitoring of disease or injury, with a special focus on the different types of healthcare data used for these applications. We then examine potential barriers to designing and integrating AI into the clinical workflow, and we propose an end-to-end framework to address these barriers and guide the development of effective AI for rehabilitation. Finally, we present ideas for future work to pave the way for AI implementation in real-world rehabilitation practices.


A CBCT based evaluation of root proximity of maxillary posterior teeth to sinus floor in a subset of Pakistani population.
To evaluate the vertical relationship of the roots of maxillary posterior teeth with maxillary sinus floor, and its association with age, gender and bilateral jaw symmetry. The cross-sectional study was conducted at a tertiary care hospital in Karachi from June to December 2018, and comprised patients who visited the dental clinics and underwent cone-beam computed tomography scans. The scans were evaluated in the axial, coronal and sagittal planes and roots were classified using Jungs classification for proximity to maxillary sinus floor. The distance between the sinus floor and the apices of maxillary posterior teeth was measured. Data was analysed using SPSS 23. There were 60 scans with 1066 roots. The most common maxillary tooth root in Type III group of Jung classification was the mesio-buccal root of the 2nd molar with the shortest mean distance of 0.44±3.05mm, followed by palatal roots of the 1st molar with the shortest mean distance of 1.58±4.01mm. The maxillary tooth root most frequent in Type I group was buccal root of 1st premolar with a mean distance of 8.15±6.65mm, and the 2nd premolar with a mean distance of 7.38±6.60mm. No significant difference was found in terms of gender and sides (p ≥0.05). The most common tooth root protruding in the sinus was found to be the mesio-buccal root of the 2nd molar, followed by palatal roots of the 1st molar. The most distant maxillary tooth root from the sinus was the buccal root of 1st and 2nd premolars.


Baculovirus replication alters hormone-regulated host development.
The baculovirus Lymantria dispar nuclear polyhedrosis virus interferes with insect larval development by altering the host's hormonal system. The level of haemolymph ecdysteroids, the insect moulting hormone, was found to be higher in virus-infected larvae than in uninfected controls. This was consistently observed in both fourth instars and day 5-infected fifth instars. The rate of hormone synthesis was examined by in vitro incubation of the prothoracic gland. Gland activity in virus-infected larvae was higher than controls and continued until the late stages of virus infection, even during the time that controls had ceased to secrete ecdysone after moulting. During virus replication, the prothoracic gland was observed to maintain morphological and ultrastructural characteristics indicative of ecdysone biosynthetic activities. Therefore, it is likely that the insects are no longer under the control of the normal hormonal system after virus infection. It is felt that the alteration of hormone titre and the rate of ecdysone synthesis is the result of the activity of ecdysteroid UDP-glucosyl transferase (EGT), a virus-encoded enzyme which is thought to inactivate ecdysteroids by sugar conjugation.


Should Public Health and Policy Communities Interact With the Food Industry? It Depends on Context Comment on "Towards Preventing and Managing Conflict of Interest in Nutrition Policy? An Analysis of Submissions to a Consultation on a Draft WHO Tool".
The issue of public health and policy communities engaging with food sector companies has long caused tension and debate. Ralston and colleagues' article 'Towards Preventing and Managing Conflict of Interest in Nutrition Policy? An Analysis of Submissions to a Consultation on a Draft WHO Tool' further examines this issue. They found widespread food industry opposition, not just to the details of the World Health Organization (WHO) tool, but to the very idea of it. In this commentary we reflect on this finding and the arguments for and against interacting with the food industry during different stages of the policy process. While involving the food industry in certain aspects of the policy process without favouring their business goals may seem like an intractable problem, we believe there are opportunities for progress that do not compromise our values as public health professionals. We suggest three key steps to making progress.


Detecting the limits of regulatory element conservation and divergence estimation using pairwise and multiple alignments.
Molecular evolutionary studies of noncoding sequences rely on multiple alignments. Yet how multiple alignment accuracy varies across sequence types, tree topologies, divergences and tools, and further how this variation impacts specific inferences, remains unclear. Here we develop a molecular evolution simulation platform, CisEvolver, with models of background noncoding and transcription factor binding site evolution, and use simulated alignments to systematically examine multiple alignment accuracy and its impact on two key molecular evolutionary inferences: transcription factor binding site conservation and divergence estimation. We find that the accuracy of multiple alignments is determined almost exclusively by the pairwise divergence distance of the two most diverged species and that additional species have a negligible influence on alignment accuracy. Conserved transcription factor binding sites align better than surrounding noncoding DNA yet are often found to be misaligned at relatively short divergence distances, such that studies of binding site gain and loss could easily be confounded by alignment error. Divergence estimates from multiple alignments tend to be overestimated at short divergence distances but reach a tool specific divergence at which they cease to increase, leading to underestimation at long divergences. Our most striking finding was that overall alignment accuracy, binding site alignment accuracy and divergence estimation accuracy vary greatly across branches in a tree and are most accurate for terminal branches connecting sister taxa and least accurate for internal branches connecting sub-alignments. Our results suggest that variation in alignment accuracy can lead to errors in molecular evolutionary inferences that could be construed as biological variation. These findings have implications for which species to choose for analyses, what kind of errors would be expected for a given set of species and how multiple alignment tools and phylogenetic inference methods might be improved to minimize or control for alignment errors.