Adolescents' Depressive Symptoms and Subsequent Technology-Based Interpersonal Behaviors: A Multi-Wave Study.
This study examined the longitudinal effects of adolescents' depressive symptoms on engagement in technology-based social comparison and feedback seeking (SCFS) behaviors. A total of 816 adolescents (54.7% girls; Mage =14.1 at Time 1) participated at three times points, each one year apart. Adolescents reported technology-based SCFS, depressive symptoms, and frequencies of technology use (cell phones, Facebook, and Instagram). Multiple group (by gender) latent growth curve models examined concurrent and lagged effects of depressive symptoms on SCFS, controlling for adolescent's underlying trajectories of SCFS and overall frequencies of technology use. Results indicated that higher levels of depressive symptoms were concurrently associated with greater SCFS after accounting for adolescents' typical patterns of SCFS. For boys only, higher depressive symptoms were prospectively associated with later increases in SCFS. Results highlight the importance of social media as a unique context in which depressed adolescents may be at risk for maladaptive interpersonal behavior.


Digital phenotyping: towards replicable findings with comprehensive assessments and integrative models in bipolar disorders.
Digital phenotyping promises to unobtrusively obtaining a continuous and objective input of symptomatology from patients' daily lives. The prime example are bipolar disorders, as smartphone parameters directly reflect bipolar symptomatology. Empirical studies, however, have yielded inconsistent findings. We believe that three main shortcomings have to be addressed to fully leverage the potential of digital phenotyping: short assessment periods, rare outcome assessments, and an extreme fragmentation of parameters without an integrative analytical strategy. To demonstrate how to overcome these shortcomings, we conducted frequent (biweekly) dimensional and categorical expert ratings and daily self-ratings over an extensive assessment period (12 months) in 29 patients with bipolar disorder. Digital phenotypes were monitored continuously. As an integrative analytical strategy, we used structural equation modelling to build latent psychopathological outcomes (mania, depression) and latent digital phenotype predictors (sleep, activity, communicativeness). Combining gold-standard categorical expert ratings with dimensional self and expert ratings resulted in two latent outcomes (mania and depression) with statistically meaningful factor loadings that dynamically varied over 299 days. Latent digital phenotypes of sleep and activity were associated with same-day latent manic psychopathology, suggesting that psychopathological alterations in bipolar disorders relate to domains (latent variables of sleep and activity) and not only to specific behaviors (such as the number of declined incoming calls). The identification of latent psychopathological outcomes that dimensionally vary on a daily basis will enable to empirically determine which combination of digital phenotypes at which days prior to an upcoming episode are viable as digital prodromal predictors.


Engineering Escherichia coli for Direct Production of 1,2-Propanediol and 1,3-Propanediol from Starch.
Diols are versatile chemicals used for multiple manufacturing products. In some previous studies, Escherichia coli has been engineered to produce 1,2-propanediol (1,2-PDO) and 1,3-propanediol (1,3-PDO) from glucose. However, there are no reports on the direct production of these diols from starch instead of glucose as a substrate. In this study, we directly produced 1,2-PDO and 1,3-PDO from starch using E. coli engineered for expressing a heterologous α-amylase, along with the expression of 1,2-PDO and 1,3-PDO synthetic genes. For this, the recombinant plasmids, pVUB3-SBA harboring amyA gene for α-amylase production, pSR5 harboring pct, pduP, and yahK genes for 1,2-PDO production, and pSR8 harboring gpd1-gpp2, dhaB123, gdrAB, and dhaT genes for 1,3-PDO production, were constructed. Subsequently, E. coli BW25113 (ΔpflA) and BW25113 strains were transformed with pVUB3-SBA, pSR5, and/or pSR8. Using these transformants, direct production of 1,2-PDO and 1,3-PDO from starch was demonstrated under microaerobic condition. As a result, the maximum production titers of 1,2-PDO and 1,3-PDO from 1% glucose as a sole carbon source were 13 mg/L and 150 mg/L, respectively. The maximum production titers from 1% starch were similar levels (30 mg/L 1,2-PDO and 120 mg/L 1,3-PDO). These data indicate that starch can be an alternative carbon source for the production of 1,2-PDO and 1,3-PDO in engineered E. coli. This technology could simplify the upstream process of diol bioproduction.


Dietary fish oil regulates gene expression of cholesterol and bile acid transporters in mice.
Fish oil rich in n-3 polyunsaturated fatty acids is known to affect hepatic lipid metabolism. Several studies have demonstrated that fish oil may affect the bile acid metabolism as well as lipid metabolism, whereas only scarce data are available. The aim of this study was to investigate the effect of fish oil on the gene expression of the transporters and enzymes related to bile acid as well as lipid metabolism in the liver and small intestine. Seven-week old male C57BL/6 mice were fed diets enriched in 10% soybean oil or 10% fish oil for 4 weeks. After 4 weeks, blood, liver and small intestine were obtained. Hepatic mRNA expression of lipids (Abcg5/8, multidrug resistance gene product 2) and bile acids transporters (bile salt export pump, multidrug resistance associated protein 2 and 3, organic solute transporter α) was induced in fish oil-fed mice. Hepatic Cyp8b1, Cyp27a1 and bile acid CoA : amino acid N-acyltransferase were increased in fish oil-fed mice compared with soybean-oil fed mice. Besides, intestinal cholesterol (Abcg5/8) and bile acid transporters (multidrug resistance associated protein 2 and organic solute transporter α) were induced in fish oil-fed mice. Fish oil induced the expression of cholesterol and bile acid transporters not only in liver but in intestine. The upregulation of Abcg5/g8 by fish oil is caused by an increase in cellular 27-HOC through Cyp27a1 induction. The hepatic induction of bile acid synthesis through Cyp27a1 may upregulate expression of bile acid transporters in both organs.


A robust active control scheme for automotive engine vibration based on disturbance observer.
In this paper, a combination of robust active controller and disturbance observer for active engine mounts is proposed as an effective way to improve driver comfort for automotive vehicles. First, a robust controller based on μ-synthesis is designed for the engine mounting system in the presence of parametric uncertainty. The effectiveness of the μ-controller in satisfying robust stability and performance is demonstrated. To further improve the performance of vibration control, an observer is designed where all system states and unknown disturbances are estimated. The estimated disturbance forces are used as control signals to cancel the unwanted effects of these disturbances. The results of the system behavior at different engine speeds clearly demonstrate a significant improvement of the system performance as a result of applying the system observer.


Effect of electron donors on anammox coupling with nitrate reduction for removing nitrogen from nitrate and ammonium.
Anammox coupling with nitrate reduction under various electron donors was studied using sludge acclimatized to have anammox and denitrification activities. Due to a deficiency in electron donors for NO(3)(-) reduction, anammox activity in an inorganic medium containing NO(3)(-) and NH(4)(+) was lower than that in NO(2)(-) and NH(4)(+). Anammox could use NO(2)(-) competitively against denitrifiers under a very limited NO(2)(-) concentration, and additions of swine wastewater or acetate stimulated anammox activity in an inorganic medium containing NO(3)(-) and NH(4)(+) with no inhibition effects. However, a high concentration of swine wastewater caused an exponential increase in denitrification activity. The addition of hydrogen and iron stimulated anammox activity in an inorganic medium containing NO(3)(-) and NH(4)(+), but iron showed an inhibitory effect on anammox in a medium containing NO(2)(-) and NH(4)(+). Hydrogen was shown to be advantageous since it did not increase denitrification even when its addition was increased.


Maturational changes of theophylline pharmacokinetics in preterm infants.
The pharmacokinetics of theophylline were studied at steady state by stable isotope methodology in nine individual preterm infants. Maturational variables such as postnatal age, postconceptional age, gestational age, duration of treatment, and body weight at the time of the study were analyzed for their influence on theophylline kinetics during the first 6 months of life. The strongest statistical correlations were found between the logarithm of theophylline half-life (t1/2) and the postnatal age (r = 0.98; p less than 0.001) and the postconceptional age (r = 0.96; p less than 0.001). Step-wise multiple regression analysis revealed postnatal age as the most powerful predictor for theophylline t1/2 in the neonatal period (partial correlation coefficients were 0.78 for postnatal age, 0.19 for postconceptional age, and 0.10 for gestational age). Gestational age, duration of treatment, and weight did not correlate significantly with any pharmacokinetic parameters. We propose that theophylline metabolizing function of the liver increases in a logarithmic fashion during the first 6 months of life.


Multi-functional Calotropis gigantea fabric using self-assembly silk fibroin, chitosan and nano-silver microspheres with oxygen low-temperature plasma treatment.
The present paper describes a novel multi-functional Calotropis gigantea (CG) fabric with durable antibacterial property and comfortable wearability for various applications. First, antibacterial microspheres (AMs) were prepared by self-assembly of silk fibroin (SF), chitosan (CS) and nano-silver microspheres (NSMs). Oxygen low-temperature plasma (OLTP) treatment was used to improve the adhesion between AMs and CG yarn. The AMs modified CG fabric has soft hand feeling, high moisture regain (10.37 ± 1.87%), good breathability, strong wrinkle resistance, and durable antibacterial properties. The antibacterial rate of the modified CG fabric against Escherichia coli (E. Coil) and Staphylococcus aureus (S. Aureus) is as high as 99.9 ± 0.1%, and it still has an antibacterial activity after washing 20 times (90.24 ± 0.65% and 80.25 ± 1.14%, respectively). The in vivo biocompatibility test showed clear signs of angiogenesis at the implantation site in the rats. Thus, this study offers the foundation for the development of functional CG fiber-based biomedical textiles.


A liquid chromatography-high resolution mass spectrometry method for the determination of thirty-three per- and polyfluoroalkyl substances in animal liver.
An analytical method for the quantification of thirty-three perfluoroalkyl and polyfluoroalkyl substances (PFASs) in animal liver was developed applying the isotopic dilution methodology with twenty-one labelled isotopologues of native compounds. The proposed protocol involved the determination of short and long aliphatic chain PFASs (C4C18) extracting liver with acetonitrile followed by two clean-up steps. The instrumental analysis was performed with liquid chromatography coupled to high-resolution mass spectrometry. The acquisition method combined full MS/dd-MS2, t-SIM/dd-MS2 and SIM experiments with variable resolution in order to maximize in one chromatographic run accuracy, sensitivity and selectivity. An eight-level validation study was performed evaluating linearity, trueness, precision, quantification and detection limits. Trueness was from 94 to 126% with intra-laboratory reproducibility lower than 20%. Limits of quantification were in the range 2-100 pg g-1, except for 2,3,3,3-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)-propanoic acid, HFPO-DA (500 pg g-1). The analysis of a certified reference material (IRMM-427) and participation in a proficiency test scheme (FAPAS - 0687) confirmed these satisfactory performances. Finally, the application of the developed procedure to detect PFASs in sixteen liver samples of farm animals revealed that chicken was the less contaminated species.


The triangular fibrocartilage complex: an important component of the pulley for the ulnar wrist extensor.
The extensor carpi ulnaris (ECU) tendon is the only wrist motor tendon that broadly connects with the triangular fibrocartilage complex (TFCC) of the wrist. The goal of this study was to determine the biomechanical effect of the TFCC on the function of the ECU. The effect of avulsion of the TFCC on the changes in mechanics of the ulnar wrist extensor tendon was investigated in 8 fresh-frozen cadaver forearms. Excursion of the ECU tendon was continuously recorded over the functional range of wrist extension and ulnar deviation in intact wrists, wrists with ulnar styloid fractures, wrists with TFCC release from the distal ulna, and after excising the distal ECU tendon sheath. The ECU tendon demonstrated a 30% increase in excursion during wrist extension after release of the TFCC from its attachment on the distal ulna. During 60 degrees of wrist extension, excursion of the ECU tendon was 4.8+/-1.9 mm in the intact wrists and 6.3+/-2.0 mm after TFCC release. This change in excursion represented 1.4 mm of bowstringing for the ECU tendon during 60 degrees of wrist extension. Further incision of the distal part of the extensor sheath produced only 6% increase in excursion of the ECU. Results of this study suggest that the TFCC is an important component of the pulley for the ulnar wrist extensor. These findings imply that disturbance of the wrist extensor after TFCC injury may potentially contribute to abnormal loading and force transmission through the ulnar wrist and the TFCC, and support the growing consensus that integrity of the TFCC should be restored in the presence of TFCC injuries.


Glycolic acid-based deep eutectic solvents boosting co-production of xylo-oligomers and fermentable sugars from corncob and the related kinetic mechanism.
Xylo-oligomers are a kind of high value-added products in biomass fractionation. Although there are several chemical methods to obtain xylo-oligomers from biomass, the reports about the deep eutectic solvents (DESs)-mediated co-production of xylo-oligomers and fermentable sugars and the related kinetic mechanism are limited. In this work, glycolic acid-based DESs were used to obtain xylo-oligomers from corncob. The highest xylo-oligomers yield of 65.9% was achieved at 120 °C for 20 min, of which the functional xylo-oligosaccharides (XOSs, DP 2-5) accounted for up to 31.8%. Meanwhile, the enzymatic digestion of cellulose and xylan in residues reached 81.0% and 95.5%, respectively. Moreover, the addition of metal inorganic salts significantly accelerated the hydrolysis of xylan and even the degradation of xylo-oligomers in DES, thus resulting in higher selectivity of xylan removal. AlCl3 showed the strongest synergistic effect with DES on accelerating the processes, while FeCl2 is best one for xylo-oligomers accumulation, affording the highest xylo-oligomers yield of 66.1% for only 10 min. Furthermore, the kinetic study indicates that the 'potential hydrolysis degree' model could well describe the xylan hydrolysis processes and glycolic acid/lactic acid (3:1) is a promising solvent for xylo-oligomers production, in particular, it worked well with FeCl2 for the excellent accumulation of xylo-oligomers. Glycolic acid-based deep eutectic solvents can be successfully applied in corncob fractionation with excellent xylo-oligomers and fermentable sugars yields on mild conditions, and the large amount of xylo-oligosaccharides accumulation could be achieved by specific process controlling. The strategies established here can be useful for developing high-valued products from biomass.


Long term results of comparison of concurrent low-dose daily cisplatin versus the standard weekly cisplatin with six fractions per week radiotherapy in locally advanced head neck cancer.
Weekly administration of cisplatin (cis-diamminedichloroplatinum [CDDP]) appears more feasible and substantially more popular than the 3 weekly schedules due to better compliance. Different concurrent cisplatin schedules have been attempted including a daily schedule. We did a comparison of two consecutive single arm studies, i.e., use of weekly cisplatin versus daily cisplatin when used with concurrently with a moderately accelerated radiotherapy (RT) schedule. Two prospective feasibility, safety and efficacy studies were carried out consecutively within the department. The weekly CDDP study was done from August 2003 to August 2005 and daily CDDP study was conducted from November 2005 to June 2007. Both studies included locally advanced stage III and IV squamous cell carcinoma of the head and neck region with RT dose of 70 Gy. Concurrent single-agent cisplatin was administered weekly (35 mg/m(2)) in the first and daily (6 mg/m(2)) in the second study. Weekly cisplatin study had 68 and daily CDDP study had 52 patients. The median follow-up in the two studies was 93 and 63 months, respectively. Compliance in the two studies was comparable. Acute Grade III/IV mucositis and dysphagia were significantly higher in weekly cisplatin study. Late Grade II/III toxicities such as xerostomia, dysphagia, ototoxicity and nephrotoxicity were similar. The 5 years locoregional control was 18% and 25% and 5 years overall survival rate was 32% and 31% in weekly and daily cisplatin studies, respectively. Modest acceleration along with either weekly or daily cisplatin, whichever is possible in one's setup, is do-able, provided due attention is paid to patient selection and supportive care.


CYTOGENETIC INDICATORS OF ACUTE RADIATION SICKNESS (THE CHORNOBYL EXPERIENCE).
The objective of the study was to improve the biological dosimetry approach among patients with acute radiationsickness of various degrees based on the analysis of radiation-induced chromosome aberrations in peripheral bloodlymphocytes of the victims. The study was based on primary cytogenetic data obtained in May 1986 within examina-tion of the 30 clean-up workers («liquidators») having got stage I-III acute radiation sickness. Dose verificationwas performed using the cytogenetic dosimetry based on a culture of peripheral blood lymphocytes with metaphaseanalysis of chromosome aberrations. A new method of evaluating the results of patients' cytogenetic examination at the beginning of specifictherapy has been developed. Procedure was performed using a model of multiple linear regression (complex of cyto-genetic parameters) and provided a satisfactory diagnostic level (featuring a compliance with initially definedclinical and laboratory diagnoses). Overall frequency of the aberrant cells and radiation markers increased in high-er disease stages. There was a trend of the frequency growth of chromatid-type aberrations with increasing of radi-ation burden. Adequacy of the proposed method based on the regression analysis of cytogenetic results was con-firmed through the preservation of group differences in estimates of disease stage in subjects with verified diagnosis. Cytogenetic dosimetry in the scope of examination of persons exposed to ionizing radiation is an oblig-atory component of radiation sickness stage verification. The recommended method of cytogenetic data evaluationbefore and at the beginning of detoxification therapy provides a satisfactory level of diagnostics.


Accuracy of 4-Dimensional Computed Tomography for Localization in Primary Hyperparathyroidism.
The etiology of primary hyperparathyroidism (PHP) is single-gland adenoma in most patients. Imaging localization of single-gland disease allows for a focused operation. We sought to determine the accuracy of imaging for localizing a solitary parathyroid adenoma. A single-institution retrospective review was performed of adult patients with PHP undergoing parathyroidectomy from January 2017 through December 2018. Surgeon-performed ultrasound (US), four-dimensional computed tomography (4DCT), and sestamibi were assessed for localization of a parathyroid adenoma yielding a single-gland parathyroidectomy. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each imaging modality. One hundred fifty-four patients underwent parathyroidectomy for PHP during the study period, with 100 patients meeting inclusion criteria with a mean age of 61.1 (SD 10) y and 80% women. Mean calcium was 11.1 mg/dL (SD 0.7) and mean PTH was 116 pg/mL (SD 66). All 100 patients had surgeon-performed US with 17 localized, 51 patients had 4DCT with 41 (80%) localized, and 69 patients had sestamibi with 53 (77%) localized. Eighty-two patients underwent successful unilateral parathyroidectomy, 18 required bilateral neck exploration. US was the most specific imaging modality at 94%. Accuracy of imaging localization was 32% for US, 70% for sestamibi, and 86% for 4DCT. Surgeon-performed US is a highly specific imaging modality for preoperative localization of solitary parathyroid adenoma in patients with PHP. 4DCT is the most accurate imaging localization study and should be considered for patients with a nonlocalized US.


Inhibitory effect of 17 beta -estradiol on prostaglandin E2-induced phosphoinositide hydrolysis in osteoblast-like cells.
We examined the effect of estradiol on PGE2-induced phosphoinositide hydrolysis and cAMP production in cloned osteoblast-like MC3T3-E1 cells. 17 beta -Estradiol pretreatment significantly inhibited the formation of inositol phosphates induced by 10 microM PGE2 in a dose-dependent manner between 1 pM and 10 nM. This effect of 17 beta -estradiol was dependent on the time of pretreatment and submaximum inhibition was observed at 4 h. However, 17 beta -estradiol had little effect on the formation of inositol phosphates induced by 20 mM NaF, a GTP-binding protein activator. The cAMP production induced by PGE2 was not influenced by 17 beta -estradiol. These results suggest that 17 beta -estradiol modulates the signal transduction by PGE2 and that the effect seems to be exerted between PGE2 receptor and the GTP-binding protein coupled to phospholipase C in osteoblast-like MC3T3-E1 cells.


The isolation of bovine-heart cytochrome c oxidase subunits. Dependence on phospholipid and cholate-content.
The polypeptide chains of bovine-heart cytochrome c oxidase were preparatively isolated by a simple large-scale procedure based on gel permeation chromatography in the presence of sodium dodecyl sulphate. The resolution of the subunits as a function of the cholate and phospholipid content of the preparation was investigated. Cholate, and to a lesser extent, phospholipids interfere with the separation of the subunits; however, they do not prevent dissociation of the enzyme by SDS. Bovine-heart cytochrome c oxidase consists of six major subunits (estimated molecular weights in thousands: 40, 25, 20, 14, 12 and 10). In addition, the enzyme preparation contains at least five minor constituents, present in less than stoichiometric amounts. The first two of the three large subunits, all of which are hydrophobic, have amino-terminal N-formylmethionine. Subunit III, however, has a free methionine N-terminus.


Fevers in patients undergoing vaginal laser surgery.
Three patients undergoing laser surgery of the vagina developed high fevers that later regressed, one of them without treatment. The possible causes and implications of these cases are discussed.


Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra provides reduced effect of scanner for cortex volumetry with atlas-based method in healthy subjects.
This study aimed to investigate whether the effect of scanner for cortex volumetry with atlas-based method is reduced using Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) normalization compared with standard normalization. Three-dimensional T1-weighted magnetic resonance images (3D-T1WIs) of 21 healthy subjects were obtained and evaluated for effect of scanner in cortex volumetry. 3D-T1WIs of the 21 subjects were obtained with five MRI systems. Imaging of each subject was performed on each of five different MRI scanners. We used the Voxel-Based Morphometry 8 tool implemented in Statistical Parametric Mapping 8 and WFU PickAtlas software (Talairach brain atlas theory). The following software default settings were used as bilateral region-of-interest labels: "Frontal Lobe," "Hippocampus," "Occipital Lobe," "Orbital Gyrus," "Parietal Lobe," "Putamen," and "Temporal Lobe." Effect of scanner for cortex volumetry using the atlas-based method was reduced with DARTEL normalization compared with standard normalization in Frontal Lobe, Occipital Lobe, Orbital Gyrus, Putamen, and Temporal Lobe; was the same in Hippocampus and Parietal Lobe; and showed no increase with DARTEL normalization for any region of interest (ROI). DARTEL normalization reduces the effect of scanner, which is a major problem in multicenter studies.


Stabilizing catalytic pathways via redundancy: selective reduction of microalgae oil to alkanes.
A new route to convert crude microalgae oils using ZrO(2)-promoted Ni catalysts into diesel-range alkanes in a cascade reaction is presented. Ni nanoparticles catalyze the selective cleavage of the C-O of fatty acid esters, leading to the hydrogenolysis of triglycerides. Hydrogenation of the resulting fatty acids to aldehydes (rate-determining step) is uniquely catalyzed via two parallel pathways, one via aldehyde formation on metallic Ni and the second via a synergistic action by Ni and ZrO(2) through adsorbing the carboxylic groups at the oxygen vacancies of ZrO(2) to form carboxylates and subsequently abstracting the α-hydrogen atom to produce ketene, which is in turn hydrogenated to aldehydes and decarbonylated on Ni nanoparticles.


Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress.
Butein and phloretin are chalcones that are members of the flavonoid family of polyphenols. Flavonoids have well-known antioxidant and anti-inflammatory activities. In rat primary hepatocytes, we examined whether butein and phloretin affect tert-butylhydroperoxide (tBHP)-induced oxidative damage and the possible mechanism(s) involved. Treatment with butein and phloretin markedly attenuated tBHP-induced peroxide formation, and this amelioration was reversed by l-buthionine-S-sulfoximine [a glutamate cysteine ligase (GCL) inhibitor] and zinc protoporphyrin [a heme oxygenase 1 (HO-1) inhibitor]. Butein and phloretin induced both HO-1 and GCL protein and mRNA expression and increased intracellular glutathione (GSH) and total GSH content. Butein treatment activated the ERK1/2 signaling pathway and increased Nrf2 nuclear translocation, Nrf2 nuclear protein-DNA binding activity, and ARE-luciferase reporter activity. The roles of the ERK signaling pathway and Nrf2 in butein-induced HO-1 and GCL catalytic subunit (GCLC) expression were determined by using RNA interference directed against ERK2 and Nrf2. Both siERK2 and siNrf2 abolished butein-induced HO-1 and GCLC protein expression. These results suggest the involvement of ERK2 and Nrf2 in the induction of HO-1 and GCLC by butein. In an animal study, phloretin was shown to increase GSH content and HO-1 expression in rat liver and decrease carbon tetrachloride-induced hepatotoxicity. In conclusion, we demonstrate that butein and phloretin up-regulate HO-1 and GCL expression through the ERK2/Nrf2 pathway and protect hepatocytes against oxidative stress.


Are Health Care Professionals Prepared to Provide Care for Patients Who Have Experienced Female Genital Cutting? A Cross-Sectional Survey of Canadian Health Care Providers.
Health care professionals may be underprepared to address the unique needs of patients who have experienced female genital cutting. This cross-sectional survey found that health care professionals in a large Canadian city report an overall lack of knowledge and preparedness to provide care for these patients and to address issues of defibulation, reinfibulation, child safeguarding, and legalities surrounding female genital cutting. Barriers to providing quality care include lack of training and clinical exposure. Health care professionals have indicated strong interest in further training, and consolidated efforts should be made to implement culturally informed care into health professional education.


Protective immune response against Toxoplasma gondii elicited by a recombinant DNA vaccine with a novel genetic adjuvant.
Previous immunological studies from our laboratory have demonstrated the potential role of Toxoplasma gondii antigens SAG1 and GRA2 as vaccine candidates. To further evaluate the vaccine's effects, a series of recombinant DNA vaccines pVAX1-SAG1, pVAX1-GRA2 and pVAX1-SAG1-GRA2, termed pSAG1, pGRA2 and pSAG1-GRA2, respectively, were constructed. A plasmid pVAX1-S/PreS2, termed pSPreS2 encoding hepatitis B virus (HBV) surface antigen (HBsAg) S and PreS2 as a novel genetic adjuvant, was also constructed. The expression abilities of those DNA plasmids were examined in HFF cells by Western blotting. Then BALB/c mice were intramuscularly immunized with DNA plasmids and followed by challenging with the highly virulent T. gondii RH strain. The results demonstrated that the recombinant DNA vaccine pSAG1-GRA2 was capable of eliciting high levels of antibodies, a Th1 type of immune response with significant production of IFN-γ and low levels of IL-4 or IL-10 in BALB/c mice, and partial protection against the acute phase of toxoplasmosis as compared to pSAG1, pGRA2 and controls. In addition, the adjuvant pSPreS2 formulated with DNA vaccine induced a Th1 type of immune response and therefore might be a novel genetic adjuvant to DNA vaccine for further investigation.


Infant mortality: a multi-level analysis of individual and community risk factors.
This paper reports the results of an analysis of infant mortality based on a conceptual model that combines micro-level and macro-level variables taken from demographic, sociological and epidemiological research traditions. Using generalized hierarchical linear modeling techniques, we analyze 1988 and 1989 linked birth and death records for Upstate New York matched with county-level data from government and private sources. Net of health and sociodemographic risk factors. our results show that the number of per capita primary care physicians and local government expenditures on health care services and hospitals are positively linked to an increase in the probability of infant death and that our indicator of hospital facilities is negatively related to risk of death. We also find that some negative health behaviors and health resources of mothers are mediated by the local health care environment. Our results demonstrate the utility of combining perspectives from several disciplines when evaluating infant death, especially the impact of policy-related issues concerning health care service in


DYRK1A reinforces epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma via cooperatively activating STAT3 and SMAD.
Hepatocellular carcinoma (HCC) accounts for the majority of liver cancer cases, while metastasis is considered the leading cause of HCC-related death. However, the currently available treatment strategies for efficient suppression of metastasis are limited. Therefore, novel therapeutic targets to inhibit metastasis and effectively treat HCC are urgently required. Wound healing and Transwell assays were used to determine the migration and invasion abilities of HCC cells in vitro. Quantitative real-time PCR (qRT-PCR), protein array, immunofluorescence, and immunoprecipitation experiments were used to study the mechanism of DYRK1A-mediated metastasis. A tail vein metastasis model and H&E staining were utilized to assess metastatic potential in vivo. The results of the current study demonstrated that dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) was upregulated in HCC tissues compared with normal liver tissues. Additionally, the level of DYRK1A was increased in primary HCC tissues of patients with metastasis compared with those of patients without metastasis, and DYRK1A overexpression correlated with worse outcomes in liver cancer patients. Gain- and loss-of-function studies suggested that DYRK1A enhanced the invasion and migration abilities of HCC cells by promoting epithelial-mesenchymal transition (EMT). Regarding the promoting effect of DYRK1A on cell invasion, the results showed that DYRK1A was coexpressed with TGF-β/SMAD and STAT3 signalling components in clinical tumour samples obtained from patients with HCC. DYRK1A also activated TGF-β/SMAD signalling by interacting with tuberous sclerosis 1 (TSC1) and enhanced metastasis of HCC cells by activating STAT3. Furthermore, DYRK1A promoted EMT by cooperatively activating STAT3/SMAD signalling. Overall, the present study not only uncovered the promoting effect of DYRK1A on HCC metastasis and revealed the mechanism but also provided a new approach to predict and treat metastatic HCC.


In vitro porphyrin-based photodynamic therapy against mono and polyculture of multidrug-resistant bacteria isolated from integumentary infections in animals.
Multidrug-resistant (MDR) organisms have been frequently isolated from integumentary lesions of animals, and these lesions are usually infected by more than one pathogen. This study evaluated an in vitro antimicrobial photodynamic therapy (aPDT) using two water-soluble tetra-cationic porphyrins (3-H2TMeP and 4-H2TMeP) against mono and polyculture of MDR bacteria isolated from dogs, cats, and horses. Ten isolates of MDR bacteria (two of each species: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus pseudointermedius) were used to evaluate aPDT against the monoculture using a non-cytotoxic concentration of 3-H2TMeP and 4-H2TMeP porphyrins (40 µM), with 30 min of light irradiation in Gram-positive and 90 min for Gram-negative bacteria. The aPDT using the 4-H2TMeP porphyrin was also tested against five different polycultures (Coagulase positive Staphylococcus (CPS) and Pseudomonas sp.; E. coli and Proteus sp.; Pseudomonas sp. and Proteus sp.; CPS and E. coli; and CPS and Proteus sp.) for 90 min. The efficacy of both treatments was evaluated by plating the solution exposed to light or kept in the dark and counting the colonies forming units after 24 h of incubation at 37 °C. Atomic force microscope analysis was used to map bacteria morphological changes and extract adhesion force parameters from the bacteria membranes. Only the 4-H2TMeP porphyrin had antibacterial activity against MDR bacteria in monoculture, especially S. pseudointermedius and P. aeruginosa. In polyculture, the 4-H2TMeP porphyrin reduced bacterial concentrations (p < 0.05) in the associations of E. coli and S. pseudointermedius, P. aeruginosa and S. pseudointermedius, and P. aeruginosa and P. mirabilis. These results showed that aPDT using 4-H2TMeP is a good option for future associations of aPDT and other therapies or in vivo research.


Temporal transcriptome features identify early skeletal commitment during human epiphysis development at single-cell resolution.
Human epiphyseal development has been mainly investigated through radiological and histological approaches, uncovering few details of cellular temporal genetic alternations. Using single-cell RNA sequencing, we investigated the dynamic transcriptome changes during post-conception weeks (PCWs) 15-25 of human distal femoral epiphysis cells. We find epiphyseal cells contain multiple subtypes distinguished by specific markers, gene signatures, Gene Ontology (GO) enrichment analysis, and gene set variation analysis (GSVA). We identify the populations committed to cartilage or ossification at this time, although the secondary ossification centers (SOCs) have not formed. We describe the temporal alternation in transcriptional expression utilizing trajectories, transcriptional regulatory networks, and intercellular communication analyses. Moreover, we find the emergence of the ossification-committed population is correlated with the COL2A1-(ITGA2/11+ITGB1) signaling. NOTCH signaling may contribute to the formation of cartilage canals and ossification via NOTCH signaling. Our findings will advance the understanding of single-cell genetic changes underlying fetal epiphysis development.


Solitary infantile gastrointestinal myofibroma: case report.
We report a case of a 7-year-old child who required emergency surgery for acute abdomen and suspected acute appendicitis. During surgery a tumor located in the small bowel that caused intestinal occlusion was found. Histopathologic analysis showed a solitary gastrointestinal myofibroma. This is a very rare tumor, especially as a single lesion, because in world literature, there are less than 10 cases reported.


Comparison of academic and practice outcomes of rural and traditional track graduates of a family medicine residency program.
The Marshall University Family Medicine Residency (MUFMR) implemented its rural track (RT) in 1994 to help achieve its mission of producing primary care physicians for practice in rural areas and West Virginia. This study examined the impact of the RT on the program's training outcomes and assessed the academic equivalence of the RT and traditional track (TT) curricula. The authors analyzed academic outcomes (in-training examination [ITE] scores, board certification rates) and practice outcomes (location and type following graduation) for the 174 MUFMR graduates who entered the program from 1984 through 2006. They compared RT and TT graduates who entered after RT implementation (1994-2006) with each other and with graduates who entered during the decade before implementation (1984-1993). There were differences between the 12 RT and 94 TT graduates in rural practice upon graduation (RT: 83% versus TT: 40%; P<.01) and practice in West Virginia (RT 83% versus TT 68%; P=.34). RT and TT graduates had similar mean increases in ITE scores and board certification rates. The 106 post-implementation graduates had a significantly higher rate of West Virginia practice than did the 68 pre-implementation graduates (70% versus 52%; P=.02). RT development was associated with a substantial increase in MUFMR graduates practicing in West Virginia. RT graduates were more likely than TT graduates to practice in rural areas and in the state upon graduation. RT graduates seem to advance academically as well as their TT counterparts.


Presbyphagia Diagnostics Using M-Mode Ultrasound: Changes in the Tongue Movement Pattern.
Age-related physiological changes of the swallowing act impair particularly the oral phase and the tongue function, which is very important for bolus preparation and transfer. At present, there are no easily applicable methods for measurement of this phase of swallowing. This study was designed to investigate the deglutitive tongue movement by M-mode ultrasound and to compare the collected parameters of different age groups. In this exploratory prospective study, the tongue and its movements of 20 younger and 30 older women were examined during swallowing by B-mode and M-mode ultrasound. Preexisting dysphagia or malnutrition as well as psychic or neurological deficits were excluded by clinical examination and screening with the Mini Nutritional Assessment-Short Form (MNA-SF), the Gugging Swallowing Screen (GUSS), the Mini-Mental State Examination (MMSE) and the Barthel Index. The data were compared with each other and statistically analyzed. With increasing age, a change in the tongue movement pattern becomes apparent. In the group of older women, the vertical lingual movement had a smaller amplitude (p < 0.001) and a shorter time to the maximum amplitude (p < 0.03) than in the group of younger women. However, there were no differences in the tongue diameter (p > 0.4). The tongue movement pattern appears to be subject to age-specific changes, in contrast to anatomy. The use of M-mode ultrasonography is an easy, radiation-free and cost-effective method for the assessment of the oral phase of swallowing. Limitations are the widely scattered values of the ultrasound findings. Further studies are needed for validation and definition of standard values for this promising method.


[Ineffectiveness of bacterial insecticides against egg laying by female mosquitoes].
Insecticides on the base of Bacillus thuringiensis and B. sphaericus proved to be ineffective against laying of eggs by female mosquitoes in the water containing these formulations.


Platelet-activating factor acetylhydrolase gene mutation in Japanese nephrotic children.
Platelet-activating factor (PAF) may be involved in the pathogenesis of steroid-responsive nephrotic syndrome (SRNS). PAF is degraded to inactive products by PAF acetylhydrolase. We have investigated whether PAF acetylhydrolase gene mutation is involved in SRNS in Japanese children. We identified a point mutation in the PAF acetylhydrolase gene (G994T) using the polymerase chain reaction in 101 Japanese children with SRNS and 100 healthy Japanese. There was no difference in the genotype and allele frequencies between patients with SRNS and normal controls. The mean number of relapses during the first year after onset was significantly higher in the 26 patients who were heterozygous for the mutant allele (GT) than in 75 wild-type homozygotes (GG) (2.61 +/- 1.98 vs. 1.33 +/- 1.35; P = 0.0019). We conclude that analysis of the PAF acetylhydrolase gene mutation at position 994 in Japanese children with SRNS allows the identification of patients who are more likely to have a disease relapse.


Drug target molecules to guide immunosuppression.
The individual and interindividual variability of response to immunosuppressants combined with the prevailing concept of lifelong immunosuppression following any organ transplantation motivates the search for methods to further individualize such therapy. Traditional therapeutic drug monitoring, adapting dose according to concentrations in blood, targets the pharmacokinetic variability. It has been increasingly recognized, however, that there is also a considerable variability in the response to a given concentration. Attempts to overcome this variability in response include the efforts to identify relevant targets and methods for pharmacodynamic monitoring. For several of the currently used immunosuppressants there is experimental data suggesting markers that are relevant as indicators for individual monitoring of the effects of these drugs. There are also some clinical data to support these approaches; however what is generally missing, are studies that in a prospective manner demonstrates the benefits and effects on outcome. The monitoring of antithymocyte globulin by lymphocyte subset counts is actually the only well established example of pharmacodynamic monitoring. For drugs such as MPA and mTOR inhibitors, there are candidates such as IMPDH activity expression and p70SK6 phosphorylation status, respectively. The monitoring of CNIs using assays for NFAT RGE, either alone or combined with concentration measurements, is already well documented. Even here, some further investigations relating to the categories of organ transplant, combination of immunosuppressants etc. will be requested. Although some further standardization of the assay is warranted and there is a need for specific recommendations of target levels and how to adjust dose, the NFAT RGE approach to pharmacodynamic monitoring of CNIs may be close to implementation in clinical routine.


Evaluation of Therapeutic Effect of Intratrigonal Injection of AbobotulinumtoxinA(Dysport) and Hydrodistention in Refractory Interstitial Cystitis /Bladder Pain Syndrome.
There are two brands of BotulinumtoxinA(BTXA) that commonly used in treatment of Lower Urinary Tract Disease: OnabotolinumtoxinA(Ona-BTXA) and AbobotulinumtoxinA (Abo-BTXA). The present study was conducted to assess the potential therapeutic and adverse effect of Abo-BTXA or Dysport for IC/BPS. Twenty-two out of 52 women diagnosed with IC/BPS who were refractory or had a low response to oral treatments of IC/BPS after 6 months, were included in the study. The end-point was O'Leary-Sant Score (OSS) including "symptoms" and "problem" indexes (ICSI and ICPI respectively) assessment after 1,3and 6 months after Abo-BTXA injection. Each patient underwent cystoscopy and immediately after hydrodistention received intratrigonal injections of 300 IU of Abo-BTXA (Dysport®) in30sites. The effect and side effects of this treatment over time have been investigated. Complications including high post void residual urine (PVR), bladder rupture, and urinary tract infections (UTI) were also assessed. The mean age of patients was 46.2±13.7 years and median OSS was 27.8±5.8.: After single injection ICSI, ICPI and total OSS significantly reduced in 1, 3, and 6 months follow up; rate of decrease total OSS was 39.5%, 36%, 18%, respectively. Its effect lasted up to six months and started to decrease after 1 months (p-value<0.05). Complications included urinary retention (PVR>200ml), bladder rupture, and UTI in 13.5%, 4.3%, and 18% of the patients, respectively. intravesical injection of 300IU Abo-BTX(Dysport) could be a useful approach for the treatment of patients with refractory IC/BPS in a period of six months.


Chicken Interspecies Chimerism Unveils Human Pluripotency.
Human pluripotent stem cells (hPSCs) are commonly kept in a primed state but also able to acquire a more immature naive state under specific conditions in vitro. Acquisition of naive state changes several properties of hPSCs and might affect their contribution to embryonic development in vivo. However, the lack of an appropriate animal test system has made it difficult to assess potential differences for chimera formation between naive and primed hPSCs. Here, we report that the developing chicken embryo is a permissive host for hPSCs, allowing analysis of the pluripotency potential of hPSCs. Transplantation of naive-like and primed hPSCs at matched developmental stages resulted in robust chimerism. Importantly, the ability of naive-like but not of primed hPSCs to form chimera was substantially reduced when injected at non-matched developmental stages. We propose that contribution to chick embryogenesis is an informative and versatile test to identify different pluripotent states of hPSCs.


Emerging mechanisms of telomerase reactivation in cancer.
Mutations in the promoter of human telomerase reverse transcriptase (hTERT) result in hyperactivation of hTERT. Notably, all mutations are G>A transitions, frequently found in a wide range of cancer types, and causally associated with cancer progression. Initially, the mutations were understood to reactivate hTERT by generating novel E26 transformation-specific (ETS) binding sites. Recent work reveals the role of DNA secondary structure G-quadruplexes, telomere binding factor(s), and chromatin looping in hTERT regulation. Here, we discuss these emerging findings in relation to the clinically significant promoter mutations to provide a broader understanding of the context-dependent outcomes that result in hTERT activation in normal and pathogenic conditions.


`Risk of cardiovascular disease associated with febuxostat versus allopurinol use in patients with gout: a retrospective cohort study in Korea.
Febuxostat is the drug used to treat hyperuricemia in patients with gout. Recently, the usage of Febuxostat has been controversial over the side effects in cardiovascular. The study aimed to comparatively analyze the risk of cardiovascular disease associated with febuxostat and allopurinol use in Korean patients with gout. A cohort study was conducted using national insurance claim data from the Health Insurance Review and Assessment Service (HIRA). Adult patients who were diagnosed with gout and prescribed febuxostat or allopurinol more than once from July 1, 2015, to June 30, 2018 were studied. The outcome was cardiovascular disease. Analysis was performed using Cox's proportional hazard model following 1:1 propensity score matching to estimate the hazard ratio with a 95% confidence interval. In total, 90,590 patients were defined as the final study cohort who had an average follow-up of 467 days, including 28,732 and 61,858 patients in the febuxostat and allopurinol groups, respectively. After the 1:1 propensity score matching, the risk of cardiovascular disease in the febuxostat group was significantly higher than in the allopurinol group (HR: 1.17; 95% CI: 1.10-1.24). In the sensitivity analysis, the risk of cardiovascular disease in the febuxostat group was significantly higher than in the allopurinol group (HR: 1.09; 95% CI: 1.04-1.15). However, further sensitivity analysis showed no statistically significant difference between the febuxostat group and allopurinol group after adjusting for cardiovascular disease history before the index date. Similarly, no statistically significant difference was found between the two drugs in the subgroup analysis. Febuxostat was not associated with a significantly increased risk of cardiovascular disease.


Policy, procedures, and goals at JOSA A: editorial.
Editorial policy and procedures are described for the benefit of potential authors and reviewers. These policies are described in the context of our goals for the journal.


Response to an itch-producing substance in cat. I. Cutaneous receptor populations with myelinated axons.
The purpose of this study was to determine which myelinated cutaneous receptor populations in cat are responsive to a stimulus (cowhage) that produces unambiguous pruritus in human subjects. Initial experiments using electrocutaneous stimuli demonstrated that fibers conducting as slowly as 1.5 m/s could be recorded from small fascicles of cutaneous nerves. Multiunit recordings from fascicles and nerve filaments revealed small, but significant changes in nerve firing following application of cowhage. A sample of all known myelinated receptor populations showed that each gave a response that was less than its response to adequate intensities of mechanical stimulation (n = 118). It was concluded that the slight changes in multunit discharge induced by cowhage could be accounted for by changes in mechanoreceptor behavior and hence there was no evidence to support the possibility that an unknown population of myelinated sensory fibers exists that signals pruritus. The possibility that itch is signaled by coactivation of myelinated mechanoreceptive and C-polymodal nociceptive neurons was discussed.


Pulmonary Valve Reconstruction Using Autologous Pericardium: A Promising Technique to Consider.
Pulmonary valve (PV) surgical treatment is uncommon in adults; however, when it is indicated, replacement with a prosthesis is suggested. Nevertheless, mechanical prostheses have an inherent risk of complications derived from anticoagulation and thrombosis, and biologic prostheses do not have adequate long-term durability. In this context, PV reconstruction surgery emerges as an alternative, avoiding anticoagulation and promising good durability. We present our experience with this procedure in 3 patients with severe PV insufficiency and 1 patient with severe PV stenosis.


Technical developments in the provision of school meals.
This paper first describes traditional methods of providing school meals and the difficulties associated with those methods. Newer methods including convenience products, cook-freeze and cook-chill systems are described together with their effects on microbial growth, nutrient retention and food sensory properties.


The melanocortin receptor agonist MTII augments the rewarding effect of amphetamine in ad-libitum-fed and food-restricted rats.
Numerous forms of evidence support a functional association between drug-seeking and ingestive behavior. One example is the augmentation of rewarding and cellular-activating effects of abused drugs by chronic food restriction. Within the past several years, a variety of orexigenic and anorexigenic neuropeptides that mediate adaptive responses to changes in energy balance and body weight have been identified. The involvement of these neuropeptidergic signaling systems in the modulation of drug reward has received little experimental attention. alpha-Melanocyte-stimulating hormone (alpha-MSH) and agouti-related protein, which act as agonist and antagonist, respectively, at melanocortin receptors (MCRs), are of particular interest because of their neuroanatomical distribution and opponent actions at a common receptor type. The objective of this study was to determine whether lateral ventricular (i.c.v.) injections of the MCR agonist MTII and MCR antagonist SHU9119 at doses that decrease and increase food intake, respectively, modify the rewarding effect of amphetamine. The rewarding effect of amphetamine was measured in terms of its ability to lower the threshold for lateral hypothalamic self-stimulation (LHSS) using a rate-frequency method. The modulatory effects of MTII and SHU9119 were evaluated by preceding i.c.v. amphetamine injection with i.c.v. injection of one of these MCR ligands or vehicle. Tests were conducted in both ad-libitum-fed and food-restricted subjects. SHU9119, the agouti-related protein-like antagonist, markedly increased overnight food intake of ad-libitum-fm-fed rats following i.c.v. injection of 1.0 microg and 0.5 microg. However, these injections had no effect on thresholds for LHSS tested 25 min or 60 min post-injection, nor did they alter the threshold-lowering effect of amphetamine (50 microg) tested 25 min, 100 min, or 24 h post-injection. MTII, the alpha-MSH-like agonist, suppressed overnight food intake of ad-libitum-fed rats following i.c.v. injection of 1.0 microg. MTII had no effect on thresholds for LHSS tested 60 min post-injection. However, this MCR agonist potentiated the threshold-lowering effect of amphetamine tested 100 min but not 24 h post-injection. This effect was evident in both ad-libitum-fed and food-restricted rats. These results indicate that agonist activity at MCRs potentiates amphetamine reward and that the anorexigenic neuropeptide alpha-MSH may exert this effect physiologically.


Obesity risk is associated with altered cerebral glucose metabolism and decreased μ-opioid and CB1 receptor availability.
Obesity is a pressing public health concern worldwide. Novel pharmacological means are urgently needed to combat the increase of obesity and accompanying type 2 diabetes (T2D). Although fully established obesity is associated with neuromolecular alterations and insulin resistance in the brain, potential obesity-promoting mechanisms in the central nervous system have remained elusive. In this triple-tracer positron emission tomography study, we investigated whether brain insulin signaling, μ-opioid receptors (MORs) and cannabinoid CB1 receptors (CB1Rs) are associated with risk for developing obesity. Subjects were 41 young non-obese males with variable obesity risk profiles. Obesity risk was assessed by subjects' physical exercise habits, body mass index and familial risk factors, including parental obesity and T2D. Brain glucose uptake was quantified with [18F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [11C]carfentanil and CB1Rs with [18F]FMPEP-d2. Subjects with higher obesity risk had globally increased insulin-stimulated brain glucose uptake (19 high-risk subjects versus 19 low-risk subjects), and familial obesity risk factors were associated with increased brain glucose uptake (38 subjects) but decreased availability of MORs (41 subjects) and CB1Rs (36 subjects). These results suggest that the hereditary mechanisms promoting obesity may be partly mediated via insulin, opioid and endocannabinoid messaging systems in the brain.


Free ammonia-based pretreatment enhances phosphorus release and recovery from waste activated sludge.
The recovery of phosphorus from waste activated sludge (WAS) was usually at low levels due to low phosphorus release. This study presents a novel, cost-effective and eco-friendly pretreatment method, e.g., using free ammonia (FA) to pretreat WAS, to enhance the phosphorus release from WAS. Experimental results showed that the phosphorus release from WAS was significantly increased after FA pretreatment at up to 189.4 mg NH3-N L-1 for 24 h, under which the released PO43--P (i.e. 101.6 ± 6.7 mg L-1) was higher than that pH 9 (i.e. 62.6 ± 4.54 mg L-1) and control (without pH and FA pretreatment) (i.e. 15.1 ± 1.86 mg L-1). More analysis revealed that the FA induced improvement in phosphorus release could be attributed to the disintegration of extracellular polymeric substances (EPS) and cell envelope of sludge cells. Moreover, the released phosphorus recovered as magnesium ammonium phosphate (MAP) was confirmed. The findings reported may guide engineers to develop an economic and practical strategy to enhance resources and energy recovery from WAS.


Respiratory Rate Estimation by Using ECG, Impedance, and Motion Sensing in Smart Clothing.
The needs for light-weight and soft smart clothing in homecare have been rising since the past decade. Many smart textile sensors have been developed and applied to automatic physiological and user-centered environmental status recognition. In the present study, we propose wearable multi-sensor smart clothing for homecare monitoring based on an economic fabric electrode with high elasticity and low resistance. The wearable smart clothing integrated with heterogeneous sensors is capable to measure multiple human biosignals (ECG and respiration), acceleration, and gyro information. Five independent respiratory signals (electric impedance plethysmography, respiratory induced frequency variation, respiratory induced amplitude variation, respiratory induced intensity variation, and respiratory induced movement variation) are obtained. The smart clothing can provide accurate respiratory rate estimation by using three different techniques (Naïve Bayes inference, static Kalman filter, and dynamic Kalman filter). During the static sitting experiments, respiratory induced frequency variation has the best performance; whereas during the running experiments, respiratory induced amplitude variation has the best performance. The Naïve Bayes inference and dynamic Kalman filter have shown good results. The novel smart clothing is soft, elastic, and washable and it is suitable for long-term monitoring in homecare medical service and healthcare industry.


The progression towards Alzheimer's disease described as a bistable switch arising from the positive loop between amyloids and Ca(2+).
Alzheimer's disease is a progressive neurodegenerative disorder affecting millions of people. It is characterized by the slow deposition of cerebral amyloid-β peptides in the brain and by dysregulations in neuronal Ca(2+) homeostasis. Numerous experimental studies have revealed the existence of a feed-forward loop wherein amyloids-β disturb neuronal Ca(2+) levels, which in turn affect the production of amyloids. Here, we formalize this positive loop in a minimal, qualitative model and show that it exhibits bistability. Thus, a stable steady state characterized by low levels of Ca(2+) and amyloids, corresponding to a healthy situation, coexists with another 'pathological state' where the levels of both compounds are high. The onset of the disease corresponds to the switch from the lower steady state to the higher one induced by a large-enough perturbation in either the metabolism of amyloids or the homeostasis of intracellular Ca(2+). Numerical simulations of the model reproduce a variety of experimental observations about the disease, as its irreversible character, the threshold-like transition to a severe pathology after the slow accumulation of symptoms, the effect of presenilins, the so-called 'prion-like' autocatalytic behaviour of amyloids and the inherent random character of the apparition of the disease that is well known for the sporadic form. The model thus provides a conceptual framework that could be useful when developing therapeutic protocols to slow down the progression of Alzheimer's disease.


Increase in urinary excretion of phosphates, hydroxyproline, and cAMP during acetate desoxycorticosterone + saline treatment in the rat.
We investigated the urinary excretion of phosphates, hydroxyproline, and cAMP in rats treated with desoxycorticosterone acetate (DOCA) associated with a hypersaline diet. We measured the three substances in groups with or without parathyroid or thyroid glands, or both. Urinary phosphate excretion increased greatly during the first weeks of treatment in normal rats and in rats autografted with parathyroids and lacking thyroid, and increased slightly in the groups without parathyroids. Hydroxyproline and cAMP had the same pattern; their excretion was greatest during week 2 of treatment in all groups, but these phenomena were more intense in animals with parathyroids. These fact support the conclusion that the parathyroid glands are stimulated during the start of mineralocorticoid-saline treatment.


Fiberoptic esophagogastroscopy, brushings, and biopsy in rabbits (Oryctolagus cuniculus).
The esophagus and stomach of rabbits were examined with a pediatric fiberoptic endoscope. The procedure involved general anesthesia and placement of an endotracheal airway followed by endoscopy. Photography, biopsies, and brushings for histology, cytology, and microbiological cultures were accomplished using this procedure. Rabbits were endoscoped and brushed repetitively on successive days without inducing esophagitis.


2,5-Hexanedione-induced immunomodulatory effect in mice.
The immunotoxic potential of 2,5-hexanedione (2,5-Hxdn), the end metabolite of n-hexane/methyl n-butyl ketone, was evaluated in a mouse model involving multiple pathomorphological, hematological, and immunological assays. Young adult male Swiss albino mice were given either single or seven consecutive oral doses of 0.2 X LD50 of 2.5-Hxdn. None of the treated mice exhibited any sign of hind limb weakness up to 1 week. On the eighth day, half the animals were sacrificed for initial pathomorphological studies of various organs and the other half were subjected to several immune function tests. The results revealed treatment-related reduction in cellularity of spleen, thymus, and mesentric lymph nodes and pathotoxicological changes. Further, immune function tests such as delayed-type hypersensitivity reaction, plaque-forming cell assay, phagocytosis by adherent peritoneal exudate cells, and resistance to endotoxin shock were considerably impaired. These results suggest that 2,5-Hxdn treatment causes profound impairment of immunity in mice even before the onset of peripheral neuropathy.


Morphological changes in the human corneal epithelium associated with surgical corneal clouding.
Light microscopy and electron microscopy were used to define morphological changes occurring in human corneal epithelium during surgery. No correlation was established between preoperative medication or peroperative fluids and corneal epithelial clouding. It is suggested that the changes we observed in relation to epithelial clouding were the direct result of disturbance to endothelial pump functions.


Complete Genome Sequences of Genamy16 and NovaSharks, Two Gordonia rubripertincta Bacteriophages Isolated from Soil in Southeastern Florida.
We report on two actinobacteriophages, Genamy16 and NovaSharks, that were isolated from soil in Florida using Gordonia rubripertincta NRRL B-16540. The genomes of both phages are ~65,000 bp, with similar GC contents, and, based on gene content similarity to phages in the Actinobacteriophage Database, were assigned to phage cluster DV.


Plasma N-terminal proatrial natriuretic factor can predict normal pulmonary capillary wedge pressure in cardiac transplant recipients.
Plasma N-terminal proatrial natriuretic factor (proANP) is closely related to atrial filling pressure, but this may be distorted in heart transplant recipients. The aim of this study was to examine the usefulness of proANP as a non-invasive marker of cardiac filling pressure in transplanted patients with normal to moderately elevated serum creatinine (s-creatinine). Blood was sampled at rest for analysis of proANP from 220 patients 1-13 (median 4) years after orthotopic heart transplantation undergoing routine diagnostic catheterization. In multivariate analysis proANP was significantly positively related to s-creatinine, mean pulmonary capillary wedge pressure (PCWP) and time after transplantation and negatively related to haemoglobin and cardiac index. All the patients with proANP below 1140 pmol/l had normal PCWP (<13 mmHg). The area under the receiver-operating characteristic curve for proANP for the detection of PCWP > 13 mmHg was 0.81. The positive predictive value of proANP for detection of increased PCWP was very low. A low proANP had a 100% negative predictive value for increased atrial pressure but the low positive predictive value makes proANP unsuitable as an indicator of increased atrial pressures in heart transplanted patients.


Low value of inherited thrombophilia testing among patients with stroke or transient ischemic attack: A three-year retrospective study.
Inherited thrombophilia testing in the acute inpatient setting is controversial and expensive, and rarely changes clinical management. We evaluated ordering patterns and results of inpatient inherited thrombophilia testing for patients who presented with an isolated acute ischemic stroke or transient ischemic attack (TIA) without concurrent venous thromboembolism. We retrospectively analyzed patients admitted for acute ischemic stroke or TIA between January 1st, 2019 and December 31st, 2021 at Thomas Jefferson University Hospitals in Philadelphia, PA and who underwent inherited thrombophilia testing during the hospital admission. Charts were reviewed to determine stroke risk factors, test results, and clinical management. Among 2108 patients admitted for acute ischemic stroke or TIA (including branch and central retinal artery occlusions) during the study period, the study included 249 patients (median age 49.0 years, 50.2% female) who underwent inpatient testing for factor V Leiden, prothrombin G20210A variant, hyperhomocysteinemia, PAI-1 elevation, and deficiencies of protein C and S and antithrombin. 42.2% of patients had at least one abnormal test, and among the 1035 tests ordered, 14.3% resulted abnormal. However, 28% of abnormal tests were borderline positive antigen or activity assays that likely represented false positives. There was no significant difference in the likelihood of a positive test among patients without stroke risk factors vs those with risk factors (47.1% vs 40.9%, P = .428), nor any significant difference between those under vs over age 50 years (45.7% vs 38.3%, P = .237). No patients with an abnormal result had their clinical management changed as a result. Charges for the tests totaled $468,588 USD. Inherited thrombophilia testing in the hospital immediately following isolated acute arterial ischemic stroke or TIA was associated with high rates of likely false positive results and was expensive. Positive results did not change clinical management in a single case.


Anticancer potential of myricanone, a major bioactive component of Myrica cerifera: novel signaling cascade for accomplishing apoptosis.
Extract of Myrica cerifera bark has long been fruitfully used as a hepato-protective and anti-cancer drug in various complementary and alternative systems of medicine. Myricanone, its principal bioactive compound, had also been reported to have apoptosis-promoting ability. We evaluated its anti-cancer potential in vitro in HepG2 liver cancer cells and tried to understand the signal cascades involved in accomplishing apoptosis. Further, we ascertained by using a (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay (MTT) assay if it had cytotoxic effects on normal noncancerous liver cells (WRL-68). We deployed various tools and protocols, like phase contrast, scanning electron and fluorescence microscopies, performed an annexinV-FITC/PI assay and cell cycle analysis, and estimated the reactive oxygen species (ROS) generation and mitochondrial membrane depolarization through flow cytometry. Further, analyses of cytochrome-c translocation and of HSP70 and caspase expressions were also done by using immunoblota and Enzyme linked immunosorbent assay (ELISA). Results revealed that myricanone induced apoptosis in HepG2 cells through generation of ROS, depolarization of the mitochondrial membrane, early release of cytochrome-c, down-regulation of HSP70 and activation of a caspase cascade; it had no, or insignificant, cytotoxic effects in WRL-68 cells in vitro and in mice in vivo. Thus, myricanone has great potential for use in formulating an effective drug against both hepatotoxicity and hepatocellular cancer.


Two-generation reproduction and cross-foster studies of perfluorooctanesulfonate (PFOS) in rats.
Perfluorooctanesulfonate (PFOS) is a persistent acid found widely distributed in wildlife and humans. To understand the potential reproductive and developmental effects of PFOS, a two-generation reproduction study was conducted in rats. Male and female rats were dosed via oral gavage at dose levels of 0, 0.1, 0.4, 1.6, and 3.2 mg/(kg day) for 6 weeks prior to mating, during mating, and, for females, through gestation and lactation, across two generations. Due to substantial F1 neonatal toxicity observed in the 1.6 and 3.2 mg/(kg day) groups, continuation into the second generation was limited to F1 pups from the 0, 0.1, and 0.4 mg/(kg day) groups. No adverse effects were observed in F0 females or their fetuses upon caesarean sectioning at gestation day 10. Statistically significant reductions in body-weight gain and feed consumption were observed in F0 generation males and females at dose levels of 0.4 mg/(kg day) and higher, but not in F1 adults. PFOS did not affect reproductive performance (mating, estrous cycling, and fertility); however, reproductive outcome, as demonstrated by decreased length of gestation, number of implantation sites, and increased numbers of dams with stillborn pups or with all pups dying on lactation days 1-4, was affected at 3.2 mg/(kg day) in F0 dams. These effects were not observed in F1 dams at the highest dose tested, 0.4 mg/(kg day). Neonatal toxicity in F1 pups, as demonstrated by reduced survival and body-weight gain through the end of lactation, occurred at a maternal dose of 1.6 mg/(kg day) and higher while not at dose levels of 0.1 or 0.4 mg/(kg day) or in F2 pups at the 0.1 or 0.4 mg/(kg day) dose levels tested. In addition to these adverse effects, slight yet statistically significant developmental delays occurred at 0.4 (eye opening) and 1.6 mg/(kg day) (eye opening, air righting, surface righting, and pinna unfolding) in F1 pups. Based on these data, the NOAELs were as follows: reproductive function: F0> or =3.2 and F1> or =0.4 mg/(kg day); reproductive outcome: F0=1.6 and F1> or =0.4 mg/(kg day); overall parental effects: F0=0.1 and F1> or =0.4 mg/(kg day); offspring effects: F0=0.4 and F1> or =0.4 mg/(kg day). To distinguish between maternal and pup influences contributing to the perinatal mortality observed in the two-generation study, a follow-up cross-foster study was performed. Results of this study indicated that in utero exposure to PFOS causally contributed to post-natal pup mortality, and that pre-natal and post-natal exposure to PFOS was additive with respect to the toxic effects observed in pups.


Parasagittal Cystic Lesions May Arise from the Pial Sheath around the Cortical Venous Wall.
It has been reported that perivenous cystic structures near the parasagittal dura are associated with the leakage of gadolinium-based contrast agents at 4 hours after intravenous administration. The origin of such cystic structures remains unknown. While reading many cases of MR cisternography, we noticed that some of the cystic structures appeared to connect to the perivenous subpial space. This new imaging finding might facilitate future research of the waste clearance system for the central nervous system.


Introduction to the medical professions through an innovative medical student-run pipeline program.
Underrepresented minorities (URMs) make up a disproportionately small percentage of medical school applicants, matriculants, and physicians relative to the general US population. Preprofessional pipeline programs may help introduce URMs to careers in the medical field. MiniMeds was developed as a paracurricular enrichment program that targeted URM students. The curriculum was designed and administered by medical students, and 2 trials of this program were conducted. Data were collected pre and post program through a survey that assessed knowledge of medical concepts and knowledge of and interest in careers in medicine. Attendance at program sessions correlated with baseline knowledge about medical professions. Knowledge about medical concepts increased significantly from baseline to follow-up for boys, a group significantly represented by URMs in our cohort. Median scores for knowledge of medical careers increased significantly from baseline to followup for URMs as well as for boys and girls. Preprofessional pipeline programs such as MiniMeds are able to engage and develop medical knowledge in URM students at a critical developmental age. Further evaluation and implementation of programs that incorporate medical students to actively develop and lead pipeline programs are warranted.


Low-replicating viruses and strong anti-viral immune response associated with prolonged disease control in a superinfected HIV-1 LTNP elite controller.
To study the causes for the lack of clinical progression in a superinfected HIV-1 LTNP elite controller patient. We studied host genetic, virological and immunological factors associated with viral control in a SI long term non progressor elite controller (LTNP-EC). The individual contained both viruses and maintained undetectable viral loads for >20 years and he did not express any of the described host genetic polymorphisms associated with viral control. None of four full-length gp160 recombinants derived from the LTNP-EC replicated in heterologous peripheral blood mononuclear cells. CTL responses after SI were maintained in two samples separated by 9 years and they were higher in breadth and magnitude than responses seen in most of 250 treatment naïve patients and also 25 controller subjects. The LTNP-EC showed a neutralization response, against 4 of the 6 viruses analyzed, superior to other ECs. The study demonstrated that a strong and sustained cellular and humoral immune response and low replicating viruses are associated with viral control in the superinfected LTNP-EC.


Antibody targeting to the murine lymphoma ESb-MP: increased accumulation due to reduced internalization into lymphoma cells as compared to normal lymphoid cells.
Using rat monoclonal antibody (MAb) 12-15A against the spontaneously metastasizing mouse lymphoma variant ESb-MP, we elaborated conditions for targeting. In vitro, high binding of labelled antibody to ESb-MP cells and low binding to lymphoid cells (e.g., spleen cells) was noted. In vivo, we observed pronounced accumulation in spleen, lymph nodes and bone marrow, the uptake kinetics indicating high accessibility of the target antigen in these tissues, and rapid clearance of radioactivity from blood and most normal tissues, indicating degradation of the antibody and excretion of the label. Binding to lymphoma tissue was slow but persistent, resulting in high tumor:tissue ratios only after 2-3 days. Biodistribution could be dramatically changed by pre-treatment of animals with excess cold antibody, which reduced trapping of labelled antibody in normal lymphatic tissue, leading to prolonged persistence in the blood and preferential uptake into tumor tissue. Monovalent 12-15A fragments showed less pronounced binding to lymphatic tissue, while being rapidly cleared from the circulation by virtue of their inherent tendency to bind to kidney tissue. Tumor:tissue ratios up to 56:1 were obtained by a combination of pre-treatment with unlabelled 12-15A IgG or Fab fragment, followed by injection of labelled fragment or IgG, respectively. This is interpreted on the basis of differences in the internalization and retention of antigen-antibody complexes. Pre-treatment obviously leads to a temporary blockade or removal of the target antigen, which is much more efficient with normal lymphoid cells than with tumor cells. Thus, it may become possible to target antibodies into the tumor despite concurrent antigen expression on normal tissue.


Immunohistochemical analysis of the early ontogeny of the neuropeptide Y system in rat brain.
The distribution of neuropeptide Y in the developing rat brain was studied with immunocytochemistry, using the peroxidase-antiperoxidase method. Immunoreactive perikarya were first seen on embryonic day 13 and staining of fibres appeared from embryonic day 15 onwards: perikaryal staining was generally more intense prenatally than after birth. Areas rich in neuropeptide Y immunostaining included the monoaminergic regions of the brain stem from embryonic day 13 (especially the lateral reticular nucleus and the medullary reticular formation), the dorsal mesencephalon (with spots of immunoreactivity in the outer subventricular zone at embryonic days 13 or 14 and many cells and fibres in the inferior colliculus from embryonic days 16-20) and the olfactory tubercle/ventral striatum from embryonic day 15 until birth. The period of development of cortical neurones extended from embryonic day 19 until postnatal day 21. A hitherto unreported feature unique to neuropeptide Y was the presence in certain parts of the cerebral cortex of transient cells at the base of the cortical plate bearing radial processes which transverse its width. They were present from embryonic day 17 until postnatal day 4 and were maximally developed at embryonic days 20 or 21, contributing at this age a substantial fibre projection through the immature corpus callosum. The abundance of neuropeptide Y in the prenatal rat brain suggests it may play an important role in development.


Corrigendum: Resilient and Self-Healing Hyaluronic Acid/Chitosan Hydrogel With Ion Conductivity, Low Water Loss, and Freeze-Tolerance for Flexible and Wearable Strain Sensor.
[This corrects the article DOI: 10.3389/fbioe.2022.837750.].


Update on nephrogenic systemic fibrosis.
Gadolinium-based contrast agents were for many years considered safe, but this is no longer the case. The least stable agents may trigger the development of nephrogenic systemic fibrosis (NSF), a generalized fibrotic disorder, in renal failure patients. The use of gadodiamide and gadopentetate dimeglumine is now contraindicated in Europe and Japan in patients who have a glomerular filtration rate less than 30 mL/min/1.73 m(2), including those on dialysis. The fear of NSF, however, should not lead to an enhanced MR imaging examination being denied when there is a good clinical indication to give a gadolinium-based contrast agent.


Rapid control of hemorrhage of the scalp in the patient with trauma.
The use of Leroy-Rainey clips is rapid and effective in controlling extensively bleeding wounds of the scalp. They are a valuable aid in assessment and stabilization of patients with trauma.


Clinical review: Regulation of food intake, energy balance, and body fat mass: implications for the pathogenesis and treatment of obesity.
Obesity has emerged as one of the leading medical challenges of the 21st century. The resistance of this disorder to effective, long-term treatment can be traced to the fact that body fat stores are subject to homeostatic regulation in obese individuals, just as in lean individuals. Because the growing obesity epidemic is linked to a substantial increase in daily energy intake, a key priority is to delineate how mechanisms governing food intake and body fat content are altered in an obesogenic environment. We considered all relevant published research and cited references that represented the highest quality evidence available. Where space permitted, primary references were cited. The increase of energy intake that has fueled the U.S. obesity epidemic is linked to greater availability of highly rewarding/palatable and energy-dense food. Obesity occurs in genetically susceptible individuals and involves the biological defense of an elevated body fat mass, which may result in part from interactions between brain reward and homeostatic circuits. Inflammatory signaling, accumulation of lipid metabolites, or other mechanisms that impair hypothalamic neurons may also contribute to the development of obesity and offer a plausible mechanism to explain the biological defense of elevated body fat mass. Despite steady research progress, mechanisms underlying the resistance to fat loss once obesity is established remain incompletely understood. Breakthroughs in this area may be required for the development of effective new obesity prevention and treatment strategies.


Psychological functions served by nicotine chewing gum.
All 43 participants in a smoking cessation study complete Russell's (1974) Smoking Motivation Questionnaire (SMQ) before quitting, and an equivalent Nicotine gum Questionnaire (NGQ) during cessation. The profiles of SMQ and NGQ scores were very similar, showing that nicotine gum served a range of psychological functions similar to that provided by cigarettes: stress modulation, feelings of arousal and pleasure, hand/mouth activity, and nicotine dependency. Gum scores were, however, around 45% of cigarette values, as would be expected from its lower nicotine dose. Failed quitters (less than 2 weeks abstinence, N = 15), short-term quitters (3-12 weeks abstinence, N = 14), and successful quitters (+13 weeks abstinence: N = 14), did not differ on any SMQ subscale. However, they did differ significantly on the NGQ habit subscale. Thus the development of a regular gum-chewing habit during the first week of cessation was associated with eventual success in quitting. Sex differences were also apparent, with females reporting higher sedative, stimulant, and hand/mouth activity gum-questionnaire scores than males. These findings provide evidence for the construct and content validity of the NGQ, but further studies into its criterion validity and test-retest reliability are required.


The subaxillary pedicled flap.
The subaxillary fasciocutaneous flap is a new pedicled flap designed and developed by us for resurfacing defects on the dorsum of the hand, thumb, fingers and web-spaces. The lack of mobility and inability of the patient to dress properly during transfer of a groin or hypogastric flap prompted us to develop this flap which is based on the direct cutaneous branch of the subscapular-thoracodorsal arterial axis to the lateral thoracic region. It consists of skin, subcutaneous tissue and the underlying fascia. It is located in the region of the lower half of the lateral chest wall extending from 5th to 10th rib to the mid-axillary line and can be raised without any delay. The donor defect can be closed primarily or skin grafted if necessary and can be very easily taken care of during hospitalisation. It can be nicely concealed later on in life. The subaxillary fasciocutaneous flap has been tried by us in 10 cases and the results are presented in this paper.


Controls of biomass partitioning between roots and shoots: Atmospheric CO2 enrichment and the acquisition and allocation of carbon and nitrogen in wild radish.
The effects of CO2 enrichment on plant growth, carbon and nitrogen acquisition and resource allocation were investigated in order to examine several hypotheses about the mechanisms that govern dry matter partitioning between shoots and roots. Wild radish plants (Raphanus sativus × raphanistrum) were grown for 25 d under three different atmospheric CO2 concentrations (200 ppm, 330 ppm and 600 ppm) with a stable hydroponic 150 μmol 1-1 nitrate supply. Radish biomass accumulation, photosynthetic rate, water use efficiency, nitrogen per unit leaf area, and starch and soluble sugar levels in leaves increased with increasing atmospheric CO2 concentration, whereas specific leaf area and nitrogen concentration of leaves significantly decreased. Despite substantial changes in radish growth, resource acquisition and resource partitioning, the rate at which leaves accumulated starch over the course of the light period and the partitioning of biomass between roots and shoots were not affected by CO2 treatment. This phenomenon was consistent with the hypothesis that root/shoot partitioning is related to the daily rate of starch accumulation by leaves during the photoperiod, but is inconsistent with hypotheses suggesting that root/shoot partitioning is controlled by some aspect of plant C/N balance.


Concept Analysis of Family-Centered Care of Hospitalized Pediatric Patients.
The purpose of this concept analysis is to provide a background of family-centered care of the hospitalized pediatric patient, clarify its components, and validate its significance to nursing practice and research. The concept of family-centered care in the hospital environment has been discussed in the literature for over 60 years, yet its principles remain unclear and poorly implemented. Further analysis of this concept is warranted and has the potential to promote its integration into current nursing practice by increasing awareness and clarifying the essential attributes. A systematic review of the literature yielded thousands of resources which were narrowed to a comprehensive list of 37 sources rich in valuable and applicable content. This analysis utilized the 8-step methodology of concept analysis described by Walker and Avant. The majority of research investigating the concept of family-centered care and the hospitalized pediatric patient found was focused on defining family-centered care and surveying both families and nurses on their understanding of the concept. Little research was found exploring the relationship of family-centered care with patient and family outcomes, or patient and family satisfaction. Family-centered care of the pediatric patient in the hospital environment remains an abstract concept. It is recommended as a cornerstone of modern nursing practice, yet nurses report they lack sufficient education regarding its operationalization into practice. Elucidation of characteristics coupled with education regarding principles of the concept has the potential to augment further integration of family-centered care in the hospital environment.


LSD1 Interacts with Zfp516 to Promote UCP1 Transcription and Brown Fat Program.
Zfp516, a brown fat (BAT)-enriched and cold-inducible transcription factor, promotes transcription of UCP1 and other BAT-enriched genes for non-shivering thermogenesis. Here, we identify lysine-specific demethylase 1 (LSD1) as a direct binding partner of Zfp516. We show that, through interaction with Zfp516, LSD1 is recruited to UCP1 and other BAT-enriched genes, such as PGC1α, to function as a coactivator by demethylating H3K9. We also show that LSD1 is induced during brown adipogenesis and that LSD1 and its demethylase activity is required for the BAT program. Furthermore, we show that LSD1 ablation in mice using Myf5-Cre alters embryonic BAT development. Moreover, BAT-specific deletion of LSD1 via the use of UCP1-Cre impairs the BAT program and BAT development, making BAT resemble WAT, reducing thermogenic activity and promoting obesity. Finally, we demonstrate an in vivo requirement of the Zfp516-LSD1 interaction for LSD1 function in BAT gene activation.


The H syndrome is caused by mutations in the nucleoside transporter hENT3.
The H syndrome is a recently reported autosomal-recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, short stature, hallux valgus, and fixed flexion contractures of the toe joints and the proximal interphalangeal joints. Homozygosity mapping in five consanguineous families resulted in the identification of mutations in the SLC29A3 gene, which encodes the equilibrative nucleoside transporter hENT3. Three mutations were found in 11 families of Arab and Bulgarian origin. The finding of several different mutations in a small geographic region implies that the H syndrome might be rather common. The identification of mutations in the SLC29A3 gene in patients with a mild clinical phenotype suggests that this is a largely underdiagnosed condition and strongly suggests that even oligosymptomatic individuals might have the disorder.


Pupillary attributions of college students to happy and angry faces.
As evidence for an hypothesis that pupil size plays an important role in nonverbal communication, Hess (1975) has reported that adults draw in appropriately sized pupils on his happy and angry faces task. However, he did not report a statistical test of his data. In this study, we replicated Hess' research and found congruent with his hypothesis that college students (n = 223) draw in significantly larger pupils on the happy face.


Axillo-femoral bypass steal due to subclavian artery stenosis.
Subclavian artery stenosis can cause a flow reversal-so-called steal-not only in the ipsilateral vertebral artery, but also in the internal mammary artery in patients with a history of coronary-artery bypass grafting. Subclavian artery stenosis is also associated with peripheral artery disease elsewhere. We report a novel finding of axillo-femoral bypass steal due to subclavian artery stenosis identified by vascular ultrasonography.


Correlated hit probability and cell transformation in an effect-specific track length model applied to in vitro alpha irradiation.
In estimating the risk from low doses of alpha particles such as those emitted by radon progeny, it is important to consider the correlation between cellular inactivation and transformation that can exist at the cellular level. A phenomenological model of radiation-induced cellular inactivation and transformation at this level is presented here which incorporates aspects of a state vector model of radiation carcinogenesis and of correlated hit probabilities for inactivation and transformation. The general form of the model assumes that both inactivation and initial initiation damage are produced through the interaction of sublesions induced by radiation passing through cell nuclei, with the production of sublesions governed by hit probabilities and a characteristic probability-per-unit track length. The inactivation and initiation events are partially correlated through the use of hit probabilities. In addition, promotional events are incorporated for the case of cellular transformation based on a previously published state vector model. The model provides good fits to available data on the relationship between inactivation, transformation and LET for doses of alpha above 0.1 Gy in the range of LETs commonly produced by radon and progeny; by "good fits" we mean here the ability to yield the correct shapes of dose-response data using parameter values that vary smoothly with LET and using inactivation parameters that are applied consistently between inactivation and transformation assays. The resulting model correctly predicts recent findings indicating an increased transformation frequency per surviving cell when a population receives a distribution of hits compared to irradiation where all cells receive the same number of hits.


Soft tissue surgery and scanners: applications and perspectives into clinical research.
With the advent of digital dentistry, we have more accurate intraoral scanners (IOSs) than ever before. Overcoming various difficulties with conventional impression techniques, optical IOSs are now widely used within the restorative and orthodontic specialities. In recent years, IOSs have been steadily integrated into soft tissue surgery, and guided implant surgery.The aim of this review article is to examine current applications and methodologies when using digital scanners to quantify outcomes in soft tissue surgery. In addition, advantages and disadvantages of current techniques are discussed, alongside an insight into the new perspectives generated by this technology. Areas for future research are highlighted.This overview of contemporary literature leads to the conclusion that current IOSs are sufficiently accurate for assessing and monitoring soft tissue changes; however, further studies are needed to address the complexities of scanning mobile tissues.


Down-regulation of exosomal miR-200c derived from keratinocytes in vitiligo lesions suppresses melanogenesis.
Vitiligo is a refractory disfiguring skin disease. However, the aetiology and pathogenesis of vitiligo have not been fully defined. Previous studies have shown that exosomes from normal human keratinocytes improve melanogenesis by up-regulating the expression of melanogenesis-related proteins. Several microRNAs (miRNAs) have been demonstrated to be effective in modulating melanogenesis via exosomes. In the present study, it was found that the effect of exosomes derived from keratinocytes in vitiligo lesions in regulating melanin synthesis is weakened. Furthermore, miR-200c was detected to be significantly down-regulated in exosomes from keratinocytes in vitiligo lesions. In addition, miR-200c enhanced the expression of melanogenesis-related genes via suppressing SOX1 to activate β-catenin. In conclusion, our study revealed that the effect of exosomes secreted by keratinocytes in vitiligo lesions exhibited a weaker capacity in promoting melanogenesis of melanocytes. Moreover, the expression of miR-200c, which mediates melanogenesis in exosomes secreted by keratinocytes in vitiligo lesions, is down-regulated, which may be one of the pathogenesis in vitiligo. Therefore, keratinocyte-derived exosomal miR-200c may be a potential target for the treatment of vitiligo.


First-Principles Determination of Ultralow Thermal Conductivity of monolayer WSe2.
By using first-principles calculations combined with the phonon Boltzmann transport equation, we systematically investigate the phonon transport of monolayer WSe2. Compared with other 2D materials, the monolayer WSe2 is found to have an ultralow thermal conductivity due to the ultralow Debye frequency and heavy atom mass. The room temperature thermal conductivity for a typical sample size of 1 μm is 3.935 W/m K, which is one order of magnitude lower than that of MoS2. And the room temperature thermal conductivity can be further decreased by about 95% in 10 nm sized samples. Moreover, we also find the ZA phonons have the dominant contribution to the thermal conductivity, and the relative contribution is almost 80% at room temperature, which is remarkably higher than that for monolayer MoS2. This is because the ZA phonons have longer lifetime than that of LA and TA phonons in monolayer WSe2.


Arthroscopically determined degree of injury after shoulder dislocation relates to recurrence rate.
The glenohumeral joint is the most mobile articulation in the body and the most commonly dislocated diarthrodial joint with peaks in the incidence of dislocation occurring during the second and sixth decades. Age at the time of the initial dislocation is inversely related to the recurrence rate. Traumatic anterior instability is often associated with intraarticular injuries. The frequency of injuries may increase with dislocation or subluxation episodes. We compared the frequency of lesions associated with traumatic anterior instability in patients with primary and recurrent instability. We retrospectively reviewed 96 selected patients with traumatic anterior instability treated arthroscopically between 2005 and 2008. Forty-five had arthroscopy after a first episode of dislocation (Group I) and 51 had two or more episodes of instability (Group II). We compared the frequencies and percentage of intraarticular lesions in both groups. We observed a Bankart lesion in all patients of both groups. The posterior Bankart lesion was observed more frequently in Group II than in Group I: 47% versus 28%. SLAP lesions were observed in 12% in Group I and 24% in Group II. In 10 patients in Group II, there was an associated rotator cuff tear. Patients with recurrent shoulder dislocation had a higher arthroscopic degree of injury. These patients presented more posterior labral lesions, SLAP tears, and rotator cuff pathology than patients with a first episode of shoulder dislocation. Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.


The effect of L-cysteine on the portion-selective uptake of cadmium in the renal proximal tubule.
Cadmium (Cd), co-administered with an excess of L-cysteine, accumulates rapidly in the kidneys of the rat. After subcutaneous (s.c.) injection of 3 mumol CdCl2/kg body wt the concentrations of Cd in the blood and kidneys increase with the dose of cysteine over the range 0.06-5.0 mmol/kg body wt. At cysteine doses of less than 1.5 mmol/kg body wt the ratio of the concentrations of Cd in the outer medulla and cortex of the kidney remains the same as that after the injection of Cd alone. This ratio, however, is more than doubled at dose levels of 5-10 mmol cysteine/kg body wt. Hepatic uptake of Cd is unaffected by doses of cysteine below 1.5 mmol/kg body wt but decreases markedly at higher doses. In animals that are dosed simultaneously with 5 mmol cysteine/kg body wt, renal uptake of 109Cd is known to occur in the straight segments of the proximal tubules. At a dose level of less than 1.5 mmol cysteine/kg body wt the present autoradiographical studies show that 109Cd is taken up predominantly by the proximal convoluted tubules of the kidney cortex. At the critical dose level (1.5 mmol/kg body wt), cysteine decreases the retention of Cd at the s.c. injection site, but probably has little effect on the distribution of Cd between protein and other carrier molecules in the blood. This distribution, however, is altered at higher cysteine dose levels. It is suggested that, under the latter conditions, stable Cd-cysteine complexes are formed in the blood and are filtered readily through the glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS)