Slant perception for stairs and screens: effects of sex and fatigue in a laboratory environment.
The apparent slope of a hill or staircase, termed geographical slant perception, is exaggerated in explicit awareness. Across two experiments this paper tests the use of a laboratory environment to study geographical slant perception. First, using a student-aged sample (N = 166), we examine the similarity of slant estimates in the field with those made in the laboratory using life-sized images of the built environment as stimuli. Results reveal no differences in slant estimates between the two test environments. Furthermore, three traditional measures of perceived geographical slant (verbal, visual, and haptic) appear sensitive to a difference in slant of only 3.4 degrees in both the field and laboratory environments. In a follow-up experiment we test the effect of fatigue on slant estimates in the laboratory. In line with previous research with outdoor stimuli, fatigued participants provided more exaggerated explicit reports of slant relative to those in a control group, and females gave more exaggerated slant estimates than males across both experiments. The current set of findings open the door to future studies of geographical slant perception that may be more suited to laboratory conditions.


Evaluation of the formation of oxidants and by-products using Pt/Ti, RuO2/Ti, and IrO2/Ti electrodes in the electrochemical process.
The aim of this study was to evaluate the formation of oxidants and by-products by using different electrode materials, such as Pt/Ti, RuO2/Ti, and IrO2/Ti, in the electrochemical process. The harmful by-products ClO3- and ClO4- were formed during the electrolysis of a Cl- electrolyte solution, as well as active chlorine, which is the most common water disinfectant. With regard to drinking water treatment, the most efficient electrode was defined as that leading to a higher formation of active chlorine and a lower formation of hazardous by-products. Overall, it was found that the Pt/Ti electrode should not be used for drinking water treatment applications, while the IrO2/Ti and RuO2/Ti electrodes are ideal for use.


Delayed rearterialization unlikely leads to nonanastomotic stricture but causes temporary injury on bile duct after liver transplantation.
Nonanastomotic strictures (NAS) are common biliary complications after liver transplantation (LT). Delayed rearterialization induces biliary injury in several hours. However, whether this injury can be prolonged remains unknown. The correlation of this injury with NAS occurrence remains obscure. Different delayed rearterialization times were compared using a porcine LT model. Morphological and functional changes in bile canaliculus were evaluated by transmission electron microscopy and real-time PCR. Immunohistochemistry and TUNEL were performed to validate intrahepatic bile duct injury. Three months after LT was performed, biliary duct stricture was determined by cholangiography; the tissue of common bile duct was detected by real-time PCR. Bile canaliculi were impaired in early postoperative stage and then exacerbated as delayed rearterialization time was prolonged. Nevertheless, damaged bile canaliculi could fully recover in subsequent months. TNF-α and TGF-β expressions and apoptosis cell ratio increased in the intrahepatic bile duct only during early postoperative period in a time-dependent manner. No abnormality was observed by cholangiography and common bile duct examination after 3 months. Delayed rearterialization caused temporary injury to bile canaliculi and intrahepatic bile duct in a time-dependent manner. Injury could be fully treated in succeeding months. Solo delayed rearterialization cannot induce NAS after LT.


Predicting energy needs in obese patients.
Obesity has become an epidemic in the United States, with other western countries also reporting increases in incidence of obesity. With many associated comorbidities, it is the most common nutritional disorder facing the medical team. However, the assessment of macronutrient needs for nutrition support regimens in obese adults is controversial. This review summarizes existing research on popular predictive approaches, including the Harris-Benedict equation, kilocalories per kilogram, and the Ireton-Jones equations. Complications including special considerations for patients who have undergone bariatric surgeries and current evidence on hypocaloric regimens are also discussed.


A Family with Von Hippel-Lindau Syndrome: The Findings of Indium-111 Somatostatin Receptor Scintigraphy, Iodine-123 Metaiodobenzylguanidine Scintigraphy and Single Photon Emission Computerized Tomography.
Von Hippel-Lindau syndrome (VHLS) is an autosomal dominant hereditary familial disorder characterized by development of malignant and benign neoplasms. Differential diagnosis of the adrenal and pancreatic masses are difficult in patients with VHLS. Iodine-123 metaiodobenzylguanidine (I-123 MIBG) and indium-111 somatostatin receptor scintigraphies (In-111 SRS) have important roles in the differential diagnosis of adrenal and pancreatic masses in those patients. In this case report, we present the findings of I-123 MIBG single-photon emission computerized tomography (SPECT/CT) and In-111 SRS SPECT/CT in three members of a family with VHLS. In case 1, a residual neuroendocrine tumor (NET) was detected in the head of pancreas on In-111 SRS SPECT/CT images. In case 2 and 3, I-123 MIBG SPECT/CT confirmed the adrenal masses as pheochromocytoma, and the extra-adrenal mass as NET, before surgery. We thought that In-111 SRS and I-123 MIBG scan might be helpful in the routine work up of VHLS patients for diagnostic and therapeutic purposes. Hybrid SPECT/CT system may improve diagnostic accuracy of planar images since it assesses morphologic and functional information together.


Skin cancer risk affected by ultraviolet solar irradiance in Arica, Chile.
The present study analyzed the risk of skin cancer due to ultraviolet erythemal irradiance (UVery) in Arica, Chile, using measurements of the solar ultraviolet index (UVI) between 2006 and 2011. The daily maximum value by biometer Yankee Environmental Systems (YES) solar ultraviolet B (UVB)-1 was measured between 2007 and 2012, and seasonal variations were clearly observed, with higher UVI levels during the summer when UVI usually reached extreme values of >11. The maximum UVI value was 15.6 in the summer of 2008 and the minimum was 2.2 in the winter of 2008. The UVI mean values that were collected monthly at noon between 2006 and 2010 fluctuated between 13 and 6, and reached higher values in January and lower values in June and July. Thus, a seasonal UVI response was observed during the two seasons. The accumulated UVery/day was calculated between September 2006 and 2007, the time when Arica normally receives the highest UVI levels. It was also noted that 60% of the days in September demonstrated values of >3.41 kJ/m2/day, while 3.3% of cloudy days had values of <2.0 kJ/m2/day. The mean value of UVery during 2007 was 3.23 kJ/m2/day and the variation was 1.9-4.6 kJ/m2/day. These UVery values were several times higher than the minimal erythemal doses (MEDs) corresponding to the skin types most frequently observed in Chile, skin types III and IV. The MED for skin type IV was 0.60 kJ/m2. The results demonstrated that the skin cancer rate was increased due to the fact that individuals from Arica are exposed to several times more UVery than the MED for their skin type during the spring and summer seasons.


Characterization of a 4-methylbenzoate-degrading methanogenic consortium as determined by small-subunit rDNA sequence analysis.
A methanogenic consortium that degrades 4-methylbenzoate (MBA) as the sole carbon and energy source was successfully enriched in an upflow anaerobic sludge bed bioreactor and studied. Electron microscopic observation showed that long rods with a distinct collar feature resembling Desulfomonile tiedjei rods were the predominant population, and that these rods formed a close spatial orientation with Methanobrevibacter-like bacteria. In addition, thin filaments and bamboo-shaped filaments that highly resembled the acetoclastic Methanosaeta were also frequently observed. A 16S rDNA clone library was constructed for the domain Bacteria, and 20 sequence types or operational taxonomic units (OTUs) were found out of 139 clones screened. Phylogenetic analysis classified these 20 nearly full-length OTUs into the delta (50.3% of total clones) and gamma (4.3%) subdivisions of the division Proteobacteria, the green non-sulfur bacteria subdivision I (7.2%), Cytophagales (7.2%), Planctomycetes (5.7%), gram-positive low G + C group (8.6%), candidate divisions OP8, OP10 and OP11 (9.3%), and a novel candidate division MBA1 (7.2%) that had an interdivisional sequence similarity less than 75%. However, only 3 OTUs had a sequence similarity higher than 90% to known isolates or environmental 16S rDNA clones, suggesting that the microbial community was diversified and largely unidentified. In particular, those 8 OTUs found in the delta-Proteobacteria were either clustered into novel groups or showed a low sequence similarity to closely related bacteria. It is highly possible that the delta-Proteobacteria were the long rods with a distinct collar feature observed microscopically, and together with the methanogens were mainly responsible for the syntrophic degradation of MBA. The unique and novel microbial populations identified explained the requirement of a long start-up period of up to 426 d for the MBA-degrading consortium.


SU(3) quasidynamical symmetry underlying the Alhassid-Whelan arc of regularity.
The first example of an empirically manifested quasidynamical symmetry trajectory in the interior of the symmetry triangle of the interacting boson approximation model is identified for large boson numbers. Along this curve, extending from SU(3) to near the critical line of the first order phase transition, spectra exhibit nearly the same degeneracies that characterize the low energy levels of SU(3). This trajectory also lies close to the Alhassid-Whelan arc of regularity, the unique interior region of regular behavior connecting the SU(3) and U(5) vertices, thus offering a possible symmetry-based interpretation of that narrow zone of regularity amidst regions of more chaotic spectra.


Physiology and molecular biology of renal carbonic anhydrase.
Carbonic anhydrase (CA) is an important enzyme in the kidney and facilitates renal acidification by catalvzing the reversible hydration of CO2 and the dehydration of bicarbonate. Currently, 14 isoforms of CA have been identified, of which CA II, CA IV, CA XII and possibly CA XIV are expressed by the kidney. Cytosolic CA II comprises -95% of renal CA, with the remainder being membrane-associated. CA II, while being nearly ubiquitous in the body, is also expressed by a large number of nephron segments, including proximal convoluted and straight tubules, thin descending limbs of Henle's loop, thick ascending limbs of Henle's loop in some species, intercalated cells of the cortical and medullary collecting ducts, and weakly in principal cells and inner medullary collecting ducts of some species; CA II is not found in glomeruli. Most membrane-associated CA is attributed to isoform IV, which is linked to the apical membrane via a glycosylphosphatidylinositol anchor; however, there is data showing that CA IV is also localized on the basolateral membranes of proximal tubule cells. How the basolateral form is linked to the membrane is not yet understood. CA IV is expressed on the luminal membrane of proximal convoluted and straight tubules, alpha-intercalated cells of cortical and medullary collecting ducts, and all cells of initial inner medullary collecting ducts. Another membrane isoform, CA XII, is also present in the kidney and probably situated in the basolateral membrane as a single-pass transmembrane protein. One study localizes CA XII to the distal nephron, while another places it in proximal tubules and inner medullary collecting ducts; confirmatory studies are needed for CA XII. The localization of CA XIV in the kidney is still under investigation. Functional studies clearly show the importance of apical and basolateral membrane CAs in mediating bicarbonate and fluid absorption in proximal tubules and of the apical membrane CA activity in mediating H+ secretion in the collecting duct. To establish other roles for CA in the kidney will require further kinetic, functional, immunolocalization and cloning studies.


Bis[(2-pyrid-yl)(2-pyridyl-amino)-methano-lato]manganese(III) nitrate.
The Mn(III) atom in the title complex, [Mn(C(11)H(10)N(3)O)(2)]NO(3), is coordinated by the two tridentate (2-pyrid-yl)(2-pyridyl-amino)-methano-late ligands, forming a six-coordinate environment. The four pyridyl N atoms constitute the equatorial plane on which the manganese(III) ion lies; the coordination plane suffers a slight distortion as indicated by the average plane deviation of 0.058 Å. The methano-late O atoms occupy the axial positions. The coordination geometry is thus octa-hedral. In the title compound, the cations are linked by nitrate anions via N-H⋯O hydrogen bonds to form one-dimensional chains. Moreover, the one-dimensional structure is stabilized by inter-molecular edge-to-face aromatic π-π inter-actions with a center-of-inversion at a distance of ca 4.634 Å.


Insulin therapy of prediabetes suppresses TH1 associated gene expression in BB rat pancreas.
Subcutaneous insulin treatment of young diabetes prone BB rats has been shown previously to suppress the development of autoimmune diabetes. In this study the hypothesis was tested that exogenous insulin may deviate the autoimmune process by acting on the Th1/Th2 cytokine balance in the pancreas. BB rats were implanted with pellets which continuously released insulin, at 50 d of age. Three weeks later cytokine mRNA expression in the pancreas and insulitis score were determined. While in control BB rats high levels of IFNgamma mRNA were detectable by RT-PCR, insulin treatment almost completely suppressed IFNgamma mRNA levels without concomitant upregulation of counterregulatory IL-10 and TGFbeta gene expression. Insulin also suppressed gene expression of inducible nitric oxide synthase. Mean insulitis scores were decreased after insulin treatment. We conclude that the protective effects of insulin treatment may not be due to the induction of protective Th2 immune reactivity but to general downregulation of immune activation in the pancreas, and hence also of Th1 autoimmunity.


COVID-19 and Avoiding Ibuprofen. How Good Is the Evidence?
Ibuprofen is an over-the-counter medication that is used widely for the treatment of pain and fever during COVID-19 pandemic. A concern was raised regarding the safety of ibuprofen use because of its role in increasing ACE2 levels within the Renin-Angiotensin-Aldosterone system. ACE2 is the coreceptor for the entry of SARS-CoV-2 into cells, and so, a potential increased risk of contracting COVID-19 disease and/or worsening of COVID-19 infection was feared with ibuprofen use. However, available data from limited studies show administration of recombinant ACE2 improves lung damage caused by respiratory viruses, suggesting ibuprofen use may be beneficial in COVID-19 disease. At this time, there is no supporting evidence to discourage the use of ibuprofen.


Secondary Traumatic Stress and Vigor Among Neonatal Intensive Care Unit Personnel: The Moderator Role of Coping Flexibility.
The demanding and highly stressful work environment of the neonatal intensive care unit (NICU) has led to the identification of a possible psychological stress reaction among NICU nurses and physicians, termed secondary traumatic stress (STS). The current study aimed to explore the association between vigor at work (as an energy resource) and STS, while considering their association with the professional role (nurses/physicians-as a condition resource) as well as with coping flexibility (as a personal resource). In this cross-sectional study physicians and nurses working in NICUs across Israel completed a questionnaire comprising sections on demographics and professional characteristics, self-rated health, STS, coping flexibility, and vigor. Of 280 physicians and nurses approached, 70% (195) completed the questionnaire. No significant differences between nurses and physicians were found in STS adjusted for gender, being in a committed relationship, and seniority in the NICU. Vigor was negatively correlated with STS-both in the entire sample and for each professional role alone. Coping flexibility was a statistically significant moderator between vigor and STS, whereas the interaction between vigor and professional role was not significant. Specifically, the negative relationship between vigor and STS was significant when coping flexibility was more than 10.10 (61% of the participants) but not significant at lower values. The understanding of the relationship between vigor and STS, with coping flexibility as its moderator, encourages an intervention aimed at reducing stress by increasing these resources.


The role of teratology information services in screening for teratogenic exposures: challenges and opportunities.
Teratology Information Services (TIS) located throughout the world have long played a key role in screening for potential new human teratogens. Using a basic prospective cohort study design, TIS recruit pregnant women from among callers to the Services who have had an exposure of interest and at the same time identify an unexposed comparison group from the same pool of callers. Women in both groups are followed to pregnancy outcome and a range of adverse outcomes including major congenital anomalies, birth size, pregnancy loss, and preterm delivery are evaluated, while controlling for potential confounding. Particularly for rare exposures or newly marketed medications, TIS may be uniquely suited to gathering this information in a timely and efficient fashion. The primary limitation of these studies is the unknown representativeness of the volunteer sample, and the typical small to moderate sample sizes. Methods to increase the proportion of exposed pregnancies that are recruited should be developed. However, small sample size TIS studies, especially when considering new or rare exposures, often fulfill the important function of providing some reassurance to women who have already had the exposure of interest by ruling out major risks for teratogenicity, that is, on the order of thalidomide. Collaborations across TIS nationally and internationally help to address the sample size challenges. A formal collaboration between the TIS cohort study model with a case-control study design is also underway and will provide complementary strengths.


Differential depression of myocardial contractility by volatile anesthetics in vitro: comparison with uncouplers of excitation-contraction coupling.
Depression of rested state contractions (RSCs) and 0.1-0.25 Hz contractions by equianesthetic concentrations of isoflurane (2.5%), halothane (1.5%), and enflurane (3.5%) was studied in guinea pig papillary muscles in which tension development was enhanced by 0.1 microM isoproterenol. In a second series of experiments, an RSC was elicited, followed by a second contraction elicited with stimulus intervals of 300-600 ms. In both types of experiments, the results were similar. Halothane and enflurane depressed rapid initial tension development more than isoflurane. This initial tension development was also selectively depressed by 0.1 microM ryanodine, which specifically decreases Ca2+ release from the sarcoplasmic reticulum (SR). Isoflurane and also enflurane depressed a delayed and late peaking component of tension development, which was very prominent after rest and was depressed by 200 microM procaine or 500 microM benzocaine. Although isoflurane and enflurane were similar to the local anesthetics in depressing late tension, unlike the local anesthetics they prolonged the late phase of tension development as well. The late tension of the RSC is associated with Ca2+, which enters the rested myocyte on depolarization and may be transiently sequestered in the SR before release. Both early initial and late tension development are depressed to a similar degree by application of 10-20 nM nifedipine. These results emphasize the multiple differing actions of the volatile anesthetics on myocardial contractions, with halothane and isoflurane possessing distinct depressant characteristics.


Evaluation of inhibition selectivity for human cytochrome P450 2A enzymes.
Cytochrome P450 (P450) enzymes are mixed-function oxidases that catalyze the metabolism of xenobiotics and endogenous biochemicals. Selective inhibitors are needed to accurately distinguish the contributions of individual P450 enzymes in the metabolism of drugs and the activation of procarcinogens in human tissues, but very frequently these enzymes have substantial overlapping selectivity. We evaluated a chemically diverse set of nine previously identified CYP2A6 inhibitors to determine which are able to discriminate between human CYP2A enzymes CYP2A6 and the 94%-identical CYP2A13 enzyme. Inhibitor binding to recombinant purified enzyme was evaluated, and affinities were determined. K(i) values were determined for inhibition of p-nitrophenol 2-hydroxylation, a reaction accomplished by CYP2A13 and CYP2A6 with more similar catalytic efficiencies (k(cat)/K(m) 0.19 and 0.12 μM⁻¹ · min⁻¹, respectively) than hydroxylation of the classic substrate coumarin (0.11 and 0.53 μM⁻¹ · min⁻¹, respectively). Of the nine compounds assayed, only tranylcypromine and (R)-(+)-menthofuran had a greater than 10-fold preference for CYP2A6 inhibition versus CYP2A13 inhibition. Most compounds evaluated [tryptamine, 4-dimethylaminobenzaldehyde, phenethyl isothiocyanate, β-nicotyrine, (S)-nicotine, and pilocarpine] demonstrated only moderate or no preference for inhibition of one CYP2A enzyme over the other. However, 8-methoxypsoralen has a 6-fold lower K(i) for CYP2A13 than for CYP2A6. This information is useful to inform reinterpretation of previous data with these inhibitors and to guide future studies seeking to determine which human CYP2A enzyme is responsible for the in vivo metabolism of compounds in human tissues expressing both enzymes.


A Novel Method to Identify Autoantibodies against Putative Target Proteins in Serum from beta-Thalassemia Major: A Pilot Study.
Abnormal immune reactivity in patients with beta-thalassemia (beta-thal) major can be associated with poor prognosis. Immunome protein-array analysis represents a powerful approach to identify novel biomarkers. The Sengenics Immunome Protein Array platform was used for high-throughput quantification of autoantibodies in 12 serum samples collected from nine beta-thal major patients and three non-thalassemia controls, which were run together with two pooled normal sera (Sengenics Internal QC samples). To obtain more accurate and reliable results, the evaluation of the biological relevance of the shortlisted biomarkers was analyzed using an Open Target Platform online database. Elevated autoantibodies directed against 23 autoantigens on the immunome array were identified and analyzed using a penetrance fold change-based bioinformatics method. Understanding the autoantibody profile of beta-thal major patients would help to further understand the pathogenesis of the disease. The identified autoantigens may serve as potential biomarkers for the prognosis of beta-thal major.


Herniographic appearance of contralateral inguinal hernia.
In 303 adults (185 men, 118 women) with unilateral groin pain and a normal physical examination, positive contrast herniography was performed. In 32 per cent of the patients a symptomatic hernia (ipsilateral) and in 18 per cent an asymptomatic hernia (contralateral) were found. The type of hernia was indirect, direct, femoral or obturator. Indirect and direct inguinal hernias were significantly more frequent on the ipsilateral side compared with the contralateral in men with right-sided groin pain. In women with left-side groin pain femoral hernias were significantly more frequent on the ipsilateral side compared with the contralateral. The size alone could not discriminate between ipsi- and contralateral hernias. The results indicate that in most patients there is no specific radiographic appearance which can discriminate between symptomatic and asymptomatic hernias.


Circadian variation in murine hepatotoxicity to the antituberculosis agent «Isoniazide».
The circadian time is an important process affecting both pharmacokinetics and pharmacodynamics of drugs. Consequently, the desired and/or undesired effects vary according to the time of drug administration in the 24 h scale. This study investigates whether the toxicity in liver as well as oxidative stress varies according to the circadian dosing-time of isoniazid (INH) in mice. A potentially toxic INH dose (120 mg/kg) was injected by i.p. route to different groups of animals at three different circadian times: 1, 9, and 17 Zeitgeber time (ZT). INH administration at 1 ZT resulted in a maximum hepatotoxicity assessed by the significant increase in both serum transaminase (ALAT: alanine aminotransferase) and (ASAT: aspartate aminotransferase) and antioxidant enzyme activities (catalase: CAT and superoxide dismutase: SOD). The highest malondialdehyde (MDA) level indicating an induction of lipid peroxidation resulting in oxidative damage was also observed at 1 ZT. Liver histopathology from INH groups at 9 ZT and at 1 ZT showed moderate to severe cytoplasma vacuolation, hepatocyte hypertrophy, ballooning, and necrosis. The circadian variation in INH toxicity may help realize a chronotherapy protocol in humans based on the selection of the best time associated to optimal tolerance or least side effects.


Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin.
The human pathology Wilson disease (WD) is characterized by toxic copper (Cu) accumulation in brain and liver, resulting in, among other indications, mitochondrial dysfunction and apoptosis of hepatocytes. In an effort to identify novel compounds that can alleviate Cu-induced toxicity, we screened the Pharmakon 1600 repositioning library using a Cu-toxicity yeast screen. We identified 2 members of the drug class of Angiotensin II Type 1 receptor blockers (ARBs) that could increase yeast tolerance to Cu, namely Candesartan and Losartan. Subsequently, we show that specific ARBs can increase yeast tolerance to Cu and/or the chemotherapeutic agent cisplatin (Cp). The latter also induces mitochondrial dysfunction and apoptosis in mammalian cells. We further demonstrate that specific ARBs can prevent the prevalence of Cu-induced apoptotic markers in yeast, with Candesartan Cilexetil being the ARB which demonstrated most pronounced reduction of apoptosis-related markers. Next, we tested the sensitivity of a selection of yeast knockout mutants affected in detoxification of reactive oxygen species (ROS) and Cu for Candesartan Cilexetil rescue in presence of Cu. These data indicate that Candesartan Cilexetil increases yeast tolerance to Cu irrespectively of major ROS-detoxifying proteins. Finally, we show that specific ARBs can increase mammalian cell tolerance to Cu, as well as decrease the prevalence of Cu-induced apoptotic markers. All the above point to the potential of ARBs in preventing Cu-induced toxicity in yeast and mammalian cells.


Note: cavity enhanced self-absorption spectroscopy: a new diagnostic tool for light emitting matter.
We introduce the concept of Cavity Enhanced Self-Absorption Spectroscopy (CESAS), a new sensitive diagnostic tool for analyzing light-emitting samples. The technique works without an additional light source and its implementation is straight forward. In CESAS, a sample (plasma, flame, or combustion source) is located in an optically stable cavity consisting of two high reflectivity mirrors, and here it acts both as light source and absorbing medium. A modest portion of the emitted light is trapped inside the cavity, making 10(4)-10(5) cavity round trips while crossing the sample and an artificial augmentation of the path length of the absorbing medium occurs as the light transverses the cavity. Light leaking out of the cavity simultaneously provides emission and absorption features. The performance is illustrated by CESAS results on supersonically expanding pulsed hydrocarbon plasma. We expect CESAS to become a generally applicable analytical tool for real time and in situ diagnostics.


Osteonecrosis After Contralateral in Situ Prophylactic Pinning for a Slipped Capital Femoral Epiphysis: A Case Report.
We report the case of an 11-year-old girl who developed osteonecrosis of the femoral head in the radiographically normal, asymptomatic left hip that had been fixed prophylactically in the context of a slipped capital femoral epiphysis (SCFE) that had been detected on the contralateral hip. The etiology of the osteonecrosis remains unknown. This case report demonstrates that prophylactic fixation of a radiographically normal, asymptomatic hip in the context of an SCFE on the contralateral side has the potential for substantial complications. Therefore, the risk of osteonecrosis in the prophylactically pinned hip should be carefully considered because this complication may have devastating functional consequences.


Electrochemically Produced Graphene for Microporous Layers in Fuel Cells.
The microporous layer (MPL) is a key cathodic component in proton exchange membrane fuel cells owing to its beneficial influence on two-phase mass transfer. However, its performance is highly dependent on material properties such as morphology, porous structure, and electrical resistance. To improve water management and performance, electrochemically exfoliated graphene (EGN) microsheets are considered as an alternative to the conventional carbon black (CB) MPLs. The EGN-based MPLs decrease the kinetic overpotential and the Ohmic potential loss, whereas the addition of CB to form a composite EGN+CB MPL improves the mass-transport limiting current density drastically. This is reflected by increases of approximately 30 and 70 % in peak power densities at 100 % relative humidity (RH) compared with those for CB- and EGN-only MPLs, respectively. The composite EGN+CB MPL also retains the superior performance at a cathode RH of 20 %, whereas the CB MPL shows significant performance loss.


[Idiopathic femur head necrosis in the adult--results of surgical therapy].
In this paper a review is given first on the various techniques in the operative treatment of the idiopathic necrosis of the femoral head in the adult. Because of the high rate of pseudarthrosis (50%) arthrodesis is rarely done today. Decompression of the medullary space is highly successful in 80-90%, but only in stage I and II. For stage III of the disease different osteotomies of the proximal femur are recommended. Artificial joint replacement is usually done in stage IV. Our case material consists of 46 operations in 37 patients (27 endoprostheses, 16 osteotomies of the proximal femur, 3 fillings with spongiosa), artificial joint replacement was always done in stage IV, the other operations in stage III of the disease. The clinical results are better than the radiological ones; in 50% of the intertrochanteric osteotomies necrosis was progressive within 4 years after operation, in 1/3 of the endoprostheses radiological loosening and periarticular calcification developed within the same period. In consideration of the unfavorable radiological findings in our case material we are going to initiate functional examination of the femoral head, because this might lead to earlier diagnosis and because central decompression of the medullary space - which is combined with this procedure - brings about a healing quotient of 80-90% in stage I and II (Arlet und Ficat, 1968; Ficat, 1983).


Longitudinal Change in Peripheral Anterior Chamber Depth of Eyes with Angle Closure after Laser Iridotomy.
To investigate longitudinal changes in peripheral anterior chamber depth (pACD) of eyes with angle closure after laser iridotomy (LI) and factors related to prognosis. Retrospective cohort study. Eyes with primary angle closure (PAC), acute PAC, or chronic angle closure glaucoma (CACG) that underwent LI (LI group) and eyes that underwent phacoemulsification and intraocular lens insertion (PEA + IOL group) were employed. Longitudinal changes in pACD were evaluated with a scanning peripheral anterior chamber depth analyzer (SPAC) in addition to routine ophthalmic examination. Forty-eight eyes of LI groups (69.8 ± 8.5 years) and 21 eyes of PEA + IOL group (65.6 ± 12.7 years) were enrolled. Mean follow-up times of LI group and PEA + IOL group were 43.4 ± 12.7 months and 36.5 ± 2.5 months, respectively. LI significantly increased pACD as indicated by the SPAC grade change from 3.8 ± 1.1 to 4.6 ± 1.2 (p < 0.001). However, SPAC grade was gradually reduced and reached the pre-LI level by the third year of follow up. PEA + IOL also significantly increased SPAC grade from 6.7 ± 1.6 to 8.7 ± 2.0 (p < 0.001), but no time-related change was observed. Twenty-three cases of LI group presented with deterioration of glaucoma control. The type of angle closure, plateau iris configuration, peripheral anterior synechia, and glaucomatous visual field defects were significantly associated with prognosis of glaucoma after LI. Peripheral ACD is temporarily deepened by LI, but returns to the pre-LI level in approximately three years. The type of angle closure and some factors may be related to glaucoma prognosis after LI.


When the answer is a maybe: a retrospective review of indeterminate SARS-CoV-2 results and their associations.
Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcriptase polymerase chain reaction (RT-PCR) may generate indeterminate results (with a cycle threshold ≥30), requiring further investigation to determine the clinical significance. Patient variables which could predict a definitive result ('Detected'/'Not detected') post indeterminate result would aid in optimization of bed management and utilization of limited resources. A retrospective observational study of indeterminate SARS-CoV-2 results in an Irish tertiary hospital from March 2020 to March 2022 was performed to determine whether demographics, comorbidities and immunosuppression were associated with a definitive result upon subsequent investigation. Data was obtained from patient and laboratory records. Analysis of association was explored using Fisher's exact test, and predictability was tested using logistic regression. Of 411 patients with an initial indeterminate test, investigation showed that 299 (72.2%) patients had a subsequent definitive result; 29 were Detected and 270 were Not detected. In the Detected group, a prior diagnosis of COVID-19 was associated with a reduced risk of becoming Detected (crude odds ratio (COR) = 0.10, 95% CI 0.03-0.35). In the Not detected group, vaccinated patients were less likely to have a Not detected result on subsequent testing (adjusted odds ratio (AOR) = 0.57, 95% CI 0.34-0.94). Patients with previous COVID-19 infection were less likely to have a Detected result and vaccinated patients were less likely to have a Not detected result upon investigation of an indeterminate result. This study emphasizes the need for a good clinical and medical history in the management of SARS-CoV-2.


Selective Bromination of Graphene Oxide by the Hunsdiecker Reaction.
Halogenated graphenes have been attracting great attention in the recent years. The currently used methods are usually non-specific, and halogen groups are randomly distributed over the graphene. Here we demonstrate a selective graphene functionalization based on a well known reaction mechanism-Hunsdiecker reaction-applied on selective bromination of graphene oxide. The chemical analysis using various spectroscopic methods proved a high efficiency of this functionalization method. Bromination can be carried out under mild conditions without any high temperature or high pressure treatment. The chemical modification led to introduction of up to 20 wt.% of bromine covalently bonded to the graphene skeleton. The modified graphene was characterized in detail using a broad range of microscopic and spectroscopic methods and no significant contamination by reaction by-products was detected.


Chromatin remodeling mediated by Drosophila GAGA factor and ISWI activates fushi tarazu gene transcription in vitro.
GAGA factor is known to remodel the chromatin structure in concert with nucleosome-remodeling factor NURF in a Drosophila embryonic S150 extract. The promoter region of the Drosophila fushi tarazu (ftz) gene carries several binding sites for GAGA factor. Both the GAGA factor-binding sites and GAGA factor per se are necessary for the proper expression of ftz in vivo. We observed transcriptional activation of the ftz gene when a preassembled chromatin template was incubated with GAGA factor and the S150 extract. The chromatin structure within the ftz promoter was specifically disrupted by incubation of the preassembled chromatin with GAGA factor and the S150 extract. Both transcriptional activation and chromatin disruption were blocked by an antiserum raised against ISWI or by base substitutions in the GAGA factor-binding sites in the ftz promoter region. These results demonstrate that GAGA factor- and ISWI-mediated disruption of the chromatin structure within the promoter region of ftz activates transcription on the chromatin template.


Magnetic resonance imaging (MRI) findings and neuropsychological sequelae in children after severe traumatic brain injury: the role of cerebellar lesion.
We studied the relationships between magnetic resonance imaging (MRI) findings and neuropsychological sequelae in children after severe traumatic brain injury. Twenty-three children ages 7-13 years underwent MRI assessment of brain lesion topography and volume and neuropsychological evaluations, more than 1 year after sustaining severe traumatic brain injury. Most children had lesions to the corpus callosum and frontal lobes. Total lesion volume and extent of cerebral atrophy did not impact on the neuropsychological evaluation. Additional relationships were observed: left frontal lesions with lower semantic verbal fluency, right occipital lesions with lower visual recognition task scores, dyscalculia with cerebellar lesions, and cerebellar damage with lower cognitive performances and lower visual recognition memory. This study demonstrates the significance of the cerebellum's role in neuropsychological outcomes after traumatic brain injury and the importance of the lesion depth classification in predicting functional results.


Guidance of Magnetic Nanocontainers for Treating Alzheimer's Disease Using an Electromagnetic, Targeted Drug-Delivery Actuator.
The "impermeability" of the blood-brain barrier (BBB) has hindered effective treatment of central nervous system (CNS) disorders such as Alzheimer's disease (AD), which is one of the most common neurodegenerative disorders. A drug can be delivered to a targeted disease site effectively by applying a strong electromagnetic force to the conjugate of a drug and magnetic nanocontainers. This study developed a novel nanotechnology-based strategy to deliver therapeutic agents to the brain via the BBB as a possible therapeutic approach for AD. First, a novel approach for an electromagnetic actuator for guiding nanocontainers is introduced. Then, we analyzed the in vivo uptake in mice experimentally to evaluate the capacity of the nanocontainers. In the mouse model, we demonstrated that magnetic particles can cross the normal BBB when subjected to external electromagnetic fields of 28 mT (0.43 T/m) and 79.8 mT (1.39 T/m). Our study also assessed the differential effects of pulsed (0.25, 0.5, and 1 Hz) and constant magnetic fields on the transport of particles across the BBB in mice injected with magnetic nanoparticles (MNPs) via a tail vein. The applied magnetic field was either kept constant or pulsed on and off. Relative to a constant magnetic field, the rate of MNP uptake and transport across the BBB was enhanced significantly by a pulsed magnetic field. Localization inside the brain was established using fluorescent MNPs. These results using 770-nm fluorescent carboxyl magnetic nanocontainers demonstrated the feasibility of the proposed electromagnetic targeted drug delivery actuator. These results establish an effective strategy for regulating the biodistribution of MNPs in the brain through the application of an external electromagnetic field. This might be a valuable targeting system for AD diagnosis and therapy.


Response efficacy and heterogeneity of antipsychotic drugs in schizophrenia: Systemic review and meta-analysis.
This meta-analysis aimed to assess antipsychotic and placebo effects in patients with schizophrenia at the level of symptom factors. A systematic literature search up to June 2020 was undertaken and 62 studies were included, with 23,478 patients with schizophrenia at the study baseline point. We calculated mean differences with 95% confidence intervals. The comparison was made according to the study content using a continuous method with a random-effects model. Patients with schizophrenia treated by antipsychotic drugs had a significantly lower psychiatric rating scale total score; lower clinical global impression of severity; lower positive and negative syndrome scale; and lower assessment of negative symptoms total score, when compared to placebo treated patients. Patients with schizophrenia treated with an antipsychotic drug show a much greater improvement and lower inconsistency in the level of symptom factors when compared to the effects of placebo. Our findings evidence for a comparatively homogeneous outcome of the antipsychotic-treatment in improving schizophrenia symptoms. This opposes the notion of the presence of patient sub-groups with treatment non-responsive schizophrenia.


Chemotherapy-related Cardiomyopathy.
Advances in chemotherapeutic agents have resulted in significantly improved cancer survival rates. Cardiac toxicity, however, has emerged as a leading cause of morbidity, both during and years after treatment. One of the most common manifestations of cardiotoxicity is that of heart failure and left ventricular systolic dysfunction. In this review, current opinions and guidelines in this field are discussed, with particular focus on the most common culprits, the anthracyclines, and the monoclonal antibody, trastuzumab.


Dual vessel arterial spin labeling scheme for regional perfusion imaging.
Regional perfusion imaging (RPI) based on pulsed arterial spin labeling and angulated inversion slabs has been recently proposed. The technique allows mapping of individual brain perfusion territories of the major feeding arteries and could become a valuable clinical tool for evaluation of patients with cerebrovascular diseases. Here we propose a new labeling scheme for RPI where lateral and posterior circulations are labeled simultaneously. Two scans instead of three are sufficient to obtain the same perfusion territories as in the original approach, allowing for a 33% reduction in the total RPI protocol time. Moreover, the position of the inversion slabs with respect to vascular anatomy facilitates the planning and allows potentially better labeling efficiency. The new approach was tested on seven healthy volunteers and compared to the original labeling scheme. The results showed that the same perfusion territories and regional CBF values can be obtained.


PAPNET analysis of reportedly negative smears preceding the diagnosis of a high-grade squamous intraepithelial lesion or carcinoma.
One hundred fourteen cervical smears obtained from 18 women developing biopsy-proven high-grade squamous intraepithelial lesions and two with invasive squamous carcinomas were analyzed by two pathologists using the PAPNET neural network-based automated screening system (PAPNET Analyses A and B). The smears were originally reported as negative and had been previously rescreened and reclassified according to The Bethesda System. Using the PAPNET video displays of 128 potentially abnormal cellular images per smear, each reviewer (PAPNET A and B) determined whether a smear required conventional rescreening. Results of the PAPNET triage were compared with the reclassification diagnoses of the smears by conventional microscopy. PAPNET Analysis A selected eight (14%) smears reclassified as negative, 25 (69%) as atypical squamous cells of undetermined significance, and 15 (71%) as squamous intraepithelial lesions (SIL) for rescreening. In PAPNET Analysis A, two (10%) SILs were not selected for rescreening, and four (19%) were considered unsatisfactory for analysis. PAPNET Analysis B selected 21 (37%) smears reclassified as negative, 25 (69%) as atypical squamous cells of undetermined significance, and 18 (86%) as SIL for review. In PAPNET Analysis B, two (10%) SILs were missed, and one (5%) smear was unsatisfactory for analysis. Each PAPNET analysis selected smears for rescreening in 19 (95%) of 20 patients and detected SILs in 10 patients that were missed in the original screening. Using PAPNET, SILs would have been detected a median of 56 months (PAPNET A) and 62 months (PAPNET B) before their actual discovery. These preliminary data suggest that PAPNET may help detect SILs missed in routine cytologic screening.(ABSTRACT TRUNCATED AT 250 WORDS)


Scalp hair as an indicator of aluminium exposure: comparison to bone and plasma.
1. Aluminium concentrations were measured in hair, plasma and bone samples from different groups of chronic renal insufficient patients and from a control group (75 healthy volunteers plus 21 deceased subjects). A cross-sectional study with 40 haemodialysis patients and two longitudinal studies were undertaken, the first comprising of 12 home haemodialysis patients and the second 16 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). 2. Before introduction of water treatment by reverse osmosis, the hair aluminium levels of home haemodialysis patients were elevated compared to controls. Aluminium in the hair of all other groups were within the normal range. Hair aluminium levels were not related to the daily aluminium intake, nor to the cumulative aluminium intake, nor to bone and plasma aluminium concentrations. 3. Plasma aluminium concentrations in all patients were higher than in the controls. Dialysis without reverse osmosis water treatment increased aluminium plasma levels. After installation of reverse osmosis units there was a decrease in the aluminium concentrations in plasma. In CAPD patients insignificant increases in the aluminium levels in plasma were observed. When low contaminated dialysis fluid was available the plasma aluminium concentrations returned to the initial level. 4. Aluminium concentrations in bone were increased in renal insufficient patients compared with controls. Aluminium bone content increased with increasing cumulative aluminium intake by phosphate binding therapy. 5. Hair analysis is of very limited value for the diagnosis of aluminium exposure. Bone analysis is suitable for the assessment of the individual body burden.


Thrombospondin-1 inhibits endothelial cell responses to nitric oxide in a cGMP-dependent manner.
Redox signaling plays an important role in the positive regulation of angiogenesis by vascular endothelial growth factor, but its role in signal transduction by angiogenesis inhibitors is less clear. Using muscle explants in 3D culture, we found that explants from mice lacking the angiogenesis inhibitor thrombospondin-1 (TSP1) exhibit exaggerated angiogenic responses to an exogenous NO donor, which could be reversed by providing exogenous TSP1. To define the basis for inhibition by TSP1, we examined the effects of TSP1 on several proangiogenic responses of endothelial cells to NO. NO has a biphasic effect on endothelial cell proliferation. The positive effect at low doses of NO is sensitive to inhibition of cGMP signaling and picomolar concentrations of TSP1. NO stimulates both directed (chemotactic) and random (chemokinetic) motility of endothelial cells in a cGMP-dependent manner. TSP1 potently inhibits chemotaxis stimulated by NO. Low doses of NO also stimulate adhesion of endothelial cells on type I collagen in a cGMP-dependent manner. TSP1 potently inhibits this response both upstream and downstream of cGMP. NO-stimulated endothelial cell responses are inhibited by recombinant type 1 repeats of TSP1 and a CD36 agonist antibody but not by the N-terminal portion of TSP1, suggesting that CD36 or a related receptor mediates these effects. These results demonstrate a potent antagonism between TSP1 and proangiogenic signaling downstream of NO. Further elucidation of this inhibitory signaling pathway may identify new molecular targets to regulate pathological angiogenesis.


Establishing the Durability and Reliability of a Dental Bur Based on the Wear.
This paper analyzes the phenomenon that conditions the durability and reliability of a type of dental bur based on the wear of the active part and with effect on its quality. For the experimental study, a conical-cylindrical dental bur and a sample dental material in cobalt-chromium alloy, cylindrical shape, tested on a specially made experimental installation were used. In this paper, the most significant parameter was considered (loss of mass, mw, through the wear of the active part of a tested dental bur), which highlights the studied wear phenomenon. This is useful for the establishment of the durability and reliability of the dental bur by the extension of the lifetime or even optimization of its operation. The wear phenomenon of the active part of dental bur is studied based on the results and experimental data obtained in the work process that was validated by interpolation and led to polynomial functions which approximate very well the dependent parameter, mw, considered in the experimental program. The results of the interpolation showed that in the first 11 h of work, the dental bur works with high efficiency (allow optimizing operation or offering new ideas for constructive solutions), after which it can be easily decommissioned; i.e., it should be replaced with a new one (establishing some possible criteria for replacing the used dental bur).


The diagnostic utility of Self-Reporting Questionnaire (SRQ) as a screening tool for major depression in hemodialysis patients.
There is overwhelming evidence that individuals with Major Depressive Disorder (MDD) are being seriously under diagnosed and under treated. The Self-Reporting Questionnaire (SRQ) is a good screening instrument for the detection of psychiatric disorders. However, the clinical significance of SRQ as a screening test for MDD in patients on hemodialysis (HD) has yet to be elucidated. The purpose of this study was to evaluate the diagnostic utility of the SRQ in detecting MDD in a cohort of patients with end-stage renal disease (ESRD) on maintenance HD. Twenty-six patients on maintenance HD were randomly recruited and were asked to complete the SRQ. The participants were, in addition, interviewed by a psychiatrist, who had been blinded to the SRQ score. We examined the ability of SRQ to detect patients who were diagnosed to have MDD based on psychiatric assessment. Among the 26 patients assessed, four patients were diagnosed to have MDD based on current diagnostic criteria. Logistic regression analysis showed that SRQ could predict patients with MDD with adjusted odds ratio of 1.9 (CI, 1.06- 3.42). Being a female was the most important variable for having a high SRQ (F=16.9, P=0.0004). The limitations of this study include a relatively small sample size and a high rate of somatic symptoms reported in the non-depressed population that limited the positive predictive value of the SRQ. Thus, although the SRQ has a high sensitivity, the positive predictive value of the SRQ is poor at low cut offs. In conclusion, our study suggests that an ideal screening tool in patients on HD should have minimal emphasis on the somatic symptoms of MDD. Until such a tool is available, clinical assessment remains the best screening tool for MDD.


Drivers of alien species composition in bird markets across the world.
The global pet trade is a major pathway for the introduction of invasive alien species. The composition of species selected for transport is driven by market demands, which may be influenced by a combination of both historical and cultural factors. We compared Eastern (Taiwan) and Western (Australia and the Iberian Peninsula) bird markets to explore factors associated with the species composition and geographic origin of the birds for sale. We used a bespoke randomization test to compare species composition, geographic origins, and species overlap at different taxonomic levels among bird markets across countries. Alien species identified in the study accounted for more than 10% of the world's bird species. Parrots and songbirds were the most common alien bird taxa traded across all markets. In both Iberian and Australian markets, there was a strong bias toward parrots, waxbills, gamebirds, and finches. In Taiwan, species traded more than expected were parrots, waxbills, starlings, and leafbirds. Neotropical species were the most traded group in the three markets. Afrotropical species were also traded more than expected in Iberian and Australian markets, while the Taiwanese traded more alien species from neighboring Asian regions. The bird trade focuses on the same few bird groups worldwide. The composition and origin of species preferred in the Western markets may be influenced by colonial histories, cultural similarity, and strict regulations on wildlife importation, while species preferences in Eastern markets are strongly influenced by regional culture and proximity. Propagule pressure is a dominant factor influencing the success of biological invasions; it is important to recognize differences in the composition of bird markets among regions because they can translate into different invasion risks, among other factors.


GlyTouCan 1.0--The international glycan structure repository.
Glycans are known as the third major class of biopolymers, next to DNA and proteins. They cover the surfaces of many cells, serving as the 'face' of cells, whereby other biomolecules and viruses interact. The structure of glycans, however, differs greatly from DNA and proteins in that they are branched, as opposed to linear sequences of amino acids or nucleotides. Therefore, the storage of glycan information in databases, let alone their curation, has been a difficult problem. This has caused many duplicated efforts when integration is attempted between different databases, making an international repository for glycan structures, where unique accession numbers are assigned to every identified glycan structure, necessary. As such, an international team of developers and glycobiologists have collaborated to develop this repository, called GlyTouCan and is available at http://glytoucan.org/, to provide a centralized resource for depositing glycan structures, compositions and topologies, and to retrieve accession numbers for each of these registered entries. This will thus enable researchers to reference glycan structures simply by accession number, as opposed to by chemical structure, which has been a burden to integrate glycomics databases in the past.


Neurocognitive outcome of school-aged children with congenital heart disease who underwent cardiopulmonary bypass surgery: a systematic review protocol.
Over the past decades, survival rates of children born with congenital heart disease (CHD) have increased dramatically. Progress in prenatal diagnosis, less-invasive catheter techniques and perioperative intensive care as well as surgical techniques have led to an increased focus on extracardiac comorbidities, including potential neurodevelopmental sequelae associated with CHD. A growing body of literature reports impairments in early and school-age developmental outcome; however, there is a substantial variability in the spectrum of examined CHD types, assessment ages and applied test batteries. Furthermore, little information is available on executive function impairments in this population. Therefore, the aim of this systematic review is to determine the impact of CHD on intellectual outcome and executive functioning at school age and to determine risk factors for impaired outcomes by means of a systematic search. A systematic review of literature that reports neurodevelopmental outcome in children with CHD undergoing cardiopulmonary bypass surgery. Intelligence quotient or executive function scores will be considered primary outcomes. Databases such as Cochrane, EMBASE, MEDLINE and PsycINFO will be searched. The results of this systematic review will summarize the current evidence on intellectual and executive function outcome after cardiopulmonary bypass surgery in school-age children with CHD. This review will thus be the basis for better patient and parental counselling and the establishment of tailored follow-up programmes and interventional trials. In accordance with the guidelines, our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on January 9, 2019 (CRD42018086568). PROSPERO CRD42019118736 .


Nine Cases of SARS-CoV-2-PCR-positive Samples Showed No Increase of Antibodies Against SARS-CoV-2.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been affecting Hokkaido, Japan since late February 2020 until present. The aim of this study was to report the relationship between anti-SARS-CoV-2 antibody-positive and SARS-CoV-2 PCR-positive cases by analyzing anti-SARS-CoV-2 antibodies (IgG and total-Ig). Serum samples were collected from care workers and nurses in two nursing homes and two hospitals which underwent virus outbreak. All people were confirmed to be SARS-CoV-2-positive by RT-qPCR and their sera was analyzed for anti-SARS-CoV-2 antibodies (IgG and total-Ig). Although 34 out of 43 samples (79.1%) showed enough amount of anti-SARS-CoV-2 antibodies, 9 RT-qPCR -positive samples (20.9%) showed absence of anti-SARS-CoV-2 antibodies in their sera. The results that 20.9% of RT-qPCR-positive samples with SARS-CoV-2 showed absence of anti-SARS-CoV-2 antibodies provides a possibility that the innate immune reaction could eliminate the virus without activating adaptive immune reaction.


Dynamic statistical model for predicting the risk of death among older Chinese people, using longitudinal repeated measures of the frailty index: a prospective cohort study.
Frailty is a common characteristic of older people with the ageing process. We aimed to develop and validate a dynamic statistical prediction model to calculate the risk of death in people aged ≥65 years, using a longitudinal frailty index (FI). One training dataset and three validation datasets from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were used in our study. The training dataset and validation datasets 1 to 3 included data from 9,748, 7,459, 9,093 and 6,368 individuals, respectively. We used 35 health deficits to construct the FI and a longitudinal FI based on repeated measurement of FI at every wave of the CLHLS. A joint model was used to build a dynamic prediction model considering both baseline covariates and the longitudinal FI. Areas under time-dependent receiver operating characteristic curves (AUCs) and calibration curves were employed to assess the predictive performance of the model. A linear mixed-effects model used time, sex, residence (city, town, or rural), living alone, smoking and alcohol consumption to calculate a subject-specific longitudinal FI. The dynamic prediction model was built using the longitudinal FI, age, residence, sex and an FI-age interaction term. The AUCs ranged from 0.64 to 0.84, and both the AUCs and the calibration curves showed good predictive ability. We developed a dynamic prediction model that was able to update predictions of the risk of death as updated measurements of FI became available. This model could be used to estimate the risk of death in individuals aged >65 years.


A cost utility analysis of treatment options for gallstone disease: methodological issues and results.
The techniques of cost utility analysis (CUA) were used to evaluate the treatment of gallstone disease by open and laparoscopic cholecystectomy and by extracorporeal shockwave lithotripsy (ESWL). The application of the techniques in this context raised three methodological questions which are not satisfactorily resolved in the literature. The first is whether an ex ante or ex post perspective is best adopted for the measurement of quality of life (QoL). The second is the method for converting a short term deterioration in QoL followed by full health into QALYs and the reliability of the methods available. The third is the issue of indirect costs which, in the context of a temporary disease state, cannot be easily avoided. The economic evaluation found laparoscopic cholecystectomy to be generally superior than the competitor technologies (entailing lower costs and better outcomes). However, the results were sensitive to assumptions about the perspective for measuring benefits and the inclusion of indirect costs.


Toward universal coverage in Massachusetts.
This paper presents several options designed to help the Commonwealth of Massachusetts move to universal health insurance coverage. The alternatives all build upon a common base that includes an expansion of the Medicaid program, income-related tax credits, a purchasing pool, and government-sponsored reinsurance. These measures in themselves would not yield universal coverage, nor would an employer mandate by itself. We show that an individual mandate, and an employer mandate combined with an individual mandate, both would yield universal coverage with a relatively small increase in government costs relative to state gross domestic product and current health spending. The cost of an employer mandate--with a "pay or play" design--is sensitive to the payroll tax rate and base, the number and kind of exemptions, and whether workers whose employers "pay" receive discounts when they purchase health insurance. The development of these alternatives and their analyses contributed to the eventual health care compromise that emerged in Massachusetts in April 2006.


Relationship between conditional early acceptance into medical school and medical school leadership and academic performance: the Conley Scholar experience at the University of Missouri-Columbia.
The Conley Scholars Program at the University of Missouri-Columbia was created in 1987 to guarantee top flight students entrance to medical school without the frantic competition well known in undergraduate pre-med programs. The program provides greater freedom as undergraduates than most combined baccalaureate-MD programs. It is not known how this freedom and avoidance of the "pre-med syndrome" affects medical school performance and relative leadership qualities compared to traditional medical students. The goals of this study are to: a) compare relative composition and performance of Conley medical students to traditional medical students; b) assess the role of Conleys in leadership positions within medical school organizations. Using the medical school computer data files and AMCAS application files, composition, academic, and leadership data were collected regarding all medical school classes containing Conleys. Statistical analysis was performed on all data. The results suggest that: a) Conley Scholars averaged significantly higher undergraduate GPAs than other medical students; b) Conley Scholars averaged higher GPAs throughout medical school; c) Conley Scholars are more likely to hold medical school leadership roles than traditional medical students. The results confirm the value of the Conley Scholar Program. Benefits extend beyond academic achievement to encompass the development of leadership skills recognized by faculty and peers.


Coexistence of tmexCD3-toprJ1b tigecycline resistance genes with two novel bla VIM-2-carrying and bla OXA-10-carrying transposons in a Pseudomononas asiatica plasmid.
Tigecycline and carbapenems are considered the last line of defense against microbial infections. The co-occurrence of resistance genes conferring resistance to both tigecycline and carbapenems in Pseudomononas asiatica was not investigated. P. asiatica A28 was isolated from hospital sewage. Antibiotic susceptibility testing showed resistance to carbapenem and tigecycline. WGS was performed to analyze the antimicrobial resistance genes and genetic characteristics. Plasmid transfer by conjugation was investigated. Plasmid fitness costs were evaluated in Pseudomonas aeruginosa transconjugants including a Galleria mellonella infection model. Meropenem and tigecycline resistant P. asiatica A28 carries a 199, 972 bp long plasmid PLA28.4 which harbors seven resistance genes. Sequence analysis showed that the 7113 bp transposon Tn7389 is made up of a class I integron without a 5'CS terminal and a complete tni module flanked by a pair of 25bp insertion repeats. Additionally, the Tn7493 transposon, 20.24 kp long, with a complete 38-bp Tn1403 IR and an incomplete 30-bp Tn1403 IR, is made up of partial skeleton of Tn1403, a class I integron harboring bla OXA-10, and a Tn5563a transposon. Moreover, one tnfxB3-tmexC3.2-tmexD3b-toprJ1b cluster was found in the plasmid and another one in the the chromosome. Furthermore, plasmid PLA28.4 could be conjugated to P. aeruginosa PAO1, with high fitness cost. A multidrug-resistant plasmid carrying tmexCD3-toprJ1b and two novel transposons carrying bla VIM-2 and bla OXA-10 -resistant genes was found in hospital sewage, increasing the risk of transmission of antibiotic-resistant genes. These finding highlight the necessary of controlling the development and spread of medication resistance requires continuous monitoring and management of resistant microorganisms in hospital sewage.


Beat-to-beat heart rate detection by smartphone's accelerometers: validation with ECG.
Mobile phones offer the possibility to monitor and track health parameters. Our aim was to test the feasibility and accuracy of measuring beat-to-beat heart rate using smartphone accelerometers by recording the vibrations generated by the heart during its function and transmitted to the chest wall, i.e. the so-called seismocardiographic signal (SCG). 9 healthy male volunteers were studied in supine (SUP) and in standing (ST) posture. A smartphone (iPhone6, Apple) was positioned on the thorax (POS1) to acquire SCG signal. While supine, a second smartphone was positioned on the navel (POS2). The SCG signal was recorded for 3 minutes during spontaneous respiration, synchronous with 3-leads ECG. Using a fully automated algorithm based on amplitude thresholding after rectification, the characteristic peak of the SCG signal (IVC) was detected and used to compute beat-to-beat heart duration, to be compared with the corresponding RR intervals extracted from the ECG. A 100% feasibility of the approach resulted for POS1 in SUP, while 89% in POS2, and 78% for POS1 in ST. In supine, for each smartphones' position, the automated algorithm correctly identified the cardiac beats with >98% accuracy. Linear correlation (r2) with RR was very high (>0.98) in each posture and position, with no bias and narrow limits of agreement. The obtained results proved the feasibility of the proposed approach and the robustness of the applied algorithm in measuring the beat-to-beat heart rate from smartphone-derived SCG, with high accuracy compared to conventional ECG-derived measure.


Rhabdomyoblastic differentiation in malignant melanoma in adults: report of 2 cases.
Two cases of malignant melanoma are reported in adults exhibiting rhabdomyoblastic differentiation to alert pathologists to this rare variant of malignant melanoma. One of the cases presented as a metastasis in a submandibular lymph node, and the other was a primary skin melanoma. There are only a few published reports on melanocytic tumors with rhabdomyoblastic differentiation, mainly occurring in giant congenital nevi. Both cases reported here were confirmed by immunohistochemistry. Both cases were also studied by electron microscopy, and one showed distinctive ultrastructural features of striated muscle.


BERTHA: Implementation of a four-component Dirac-Kohn-Sham relativistic framework.
In this paper, we present and review the most recent computational advances in the BERTHA code. BERTHA can be regarded as the state of the art in fully relativistic four-component Dirac-Kohn-Sham (DKS) software. Thanks to the implementation of various parallelization and memory open-ended distribution schemes in combination with efficient "density fitting" algorithms, it greatly reduces the computational burden of four-component DKS calculations. We also report the newly developed OpenMP version of the code, that, together with the berthmod Python module, provides a significant leap forward in terms of usability and applicability of the BERTHA software. Some applications of the recently developed natural orbitals for chemical valence/charge displacement bonding analysis and the real-time time dependent DKS implementation are also reported.


Colorectal Cancer Prognosis is Not Associated with BRAF and KRAS Mutations-A STROBE Compliant Study.
We investigated the associations between v-Raf murine sarcoma viral oncogene homolog B1 (BRAFV600E, henceforth BRAF) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and colorectal cancer (CRC) prognosis, using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GSE39582) datasets. The effects of BRAF and KRAS mutations on overall survival (OS) and disease-free survival (DFS) of CRC were evaluated. The mutational status of BRAF and KRAS genes was not associated with overall survival (OS) or DFS of the CRC patients drawn from the TCGA database. The 3-year OS and DFS rates of the BRAF mutation (+) vs. mutation (-) groups were 92.6% vs. 90.4% and 79.7% vs. 68.4%, respectively. The 3-year OS and DFS rates of the KRAS mutation (+) vs. mutation (-) groups were 90.4% vs. 90.5% and 65.3% vs. 73.5%, respectively. In stage II patients, however, the 3-year OS rate was lower in the BRAF mutation (+) group than in the mutation (-) group (85.5% vs. 97.7%, p <0.001). The mutational status of BRAF genes of 497 CRC patients drawn from the GSE39582 database was not associated with OS or DFS. The 3-year OS and DFS rates of BRAF mutation (+) vs. mutation (-) groups were 75.7% vs. 78.9% and 73.6% vs. 71.1%, respectively. However, KRAS mutational status had an effect on 3-year OS rate (71.9% mutation (+) vs. 83% mutation (-), p = 0.05) and DFS rate (66.3% mutation (+) vs. 74.6% mutation (-), p = 0.013). We found no consistent association between the mutational status of BRAF nor KRAS and the OS and DFS of CRC patients from the TCGA and GSE39582 databases. Studies with longer-term records and larger patient numbers may be necessary to expound the influence of BRAF and KRAS mutations on the outcomes of CRC.


High-resolution temporal profiling of the human gut microbiome reveals consistent and cascading alterations in response to dietary glycans.
Dietary glycans, widely used as food ingredients and not directly digested by humans, are of intense interest for their beneficial roles in human health through shaping the microbiome. Characterizing the consistency and temporal responses of the gut microbiome to glycans is critical for rationally developing and deploying these compounds as therapeutics. We investigated the effect of two chemically distinct glycans (fructooligosaccharides and polydextrose) through three clinical studies conducted with 80 healthy volunteers. Stool samples, collected at dense temporal resolution (~ 4 times per week over 10 weeks) and analyzed using shotgun metagenomic sequencing, enabled detailed characterization of participants' microbiomes. For analyzing the microbiome time-series data, we developed MC-TIMME2 (Microbial Counts Trajectories Infinite Mixture Model Engine 2.0), a purpose-built computational tool based on nonparametric Bayesian methods that infer temporal patterns induced by perturbations and groups of microbes sharing these patterns. Overall microbiome structure as well as individual taxa showed rapid, consistent, and durable alterations across participants, regardless of compound dose or the order in which glycans were consumed. Significant changes also occurred in the abundances of microbial carbohydrate utilization genes in response to polydextrose, but not in response to fructooligosaccharides. Using MC-TIMME2, we produced detailed, high-resolution temporal maps of the microbiota in response to glycans within and across microbiomes. Our findings indicate that dietary glycans cause reproducible, dynamic, and differential alterations to the community structure of the human microbiome.


Synthesis and monoamine oxidase inhibitory activity of new pyridazine-, pyrimidine- and 1,2,4-triazine-containing tricyclic derivatives.
A number of condensed azines, mostly belonging to the families of indeno-fused pyridazines (1), pyrimidines (2, 3), and 1,2,4-triazines (4, 5), were synthesized and evaluated in vitro as monoamine oxidase (MAO) A and B inhibitors. Most of them showed higher inhibition potency toward MAO-B, the most effective one being 3-(3-nitrophenyl)-9H-indeno[1,2-e] [1,2,4]triazin-9-one (4c), which displayed an IC50 value of 80 nM and proved to be 10-fold more potent than its [2,1-e] fusion isomer 5. Replacing the 3-phenyl group of the known indeno[1,2-c]pyridazin-5-one MAO-B inhibitors with a flexible phenoxymethyl group enhanced the inhibitory potency. The inhibition data highlighted the importance of the aza-heterocyclic scaffold in affecting the MAO isoform selectivity. The 3-phenyl derivatives with type 1, 4, and 5 scaffolds were inhibitors of MAO-B with little or no MAO-A effect, whereas 2- or 3-phenyl derivatives of type 2 and 3 pyrimidine-containing fusion isomers inhibited both isoenzymes with a structure-dependent preference toward MAO-A.


Health-related quality of life among survivors in minority area 2 years after Jiuzhaigou earthquake: A cross-sectional study.
To investigate the health-related quality of life (HRQoL) and related factors, the symptoms of posttraumatic stress disorder (PTSD) among earthquake survivors in minority area 2 years after Jiuzhaigou earthquake.Two years after the Jiuzhaigou earthquake, a cross-sectional survey was conducted by a multi-stage sampling approach. HRQoL was measured by the short form 12 (SF-12), PTSD was measured by the PTSD Check List-Civilian Version (PCL-C), and social support was measured by the Multidimensional Scale of Perceived Social Support. Descriptive statistics, t-tests, ANOVA and multiple linear regression analysis were used for data analysis.Of the 561 participants, the mean scores on the physical component summary (PCS) and mental component summary (MCS) were 46.36 ± 12.79 and 55.03 ± 8.73, and 5.73% reported the symptoms of PTSD. Lower PCS and MCS after an earthquake were associated with elderly age, physical illness, and low level of social support (P < .05). Meanwhile, PTSD was significantly associated with MCS.These findings showed that physical disease and psychological symptoms can adversely affect the HRQoL of survivors. Moreover, providing higher social support to survivors should be considered as a way to improve the HRQoL outcomes of survivors.


What Does Minimally Invasive Mitral Valve Surgery Really Mean? Defining Totally Endoscopic Mitral Valve Surgery Through Meta Analysis.
Minimally invasive approaches to mitral valve surgery are being performed with increasing frequency; however, many of these procedures still involve rib spreading and large incisions. The heterogeneity of self-reported "minimally invasive" approaches limits analysis of outcomes. This review aims to formally define totally endoscopic mitral valve surgery (TEMVS) and assess outcomes. A comprehensive literature search in Pub-Med, Cochrane Library, and EMBASE was used to find studies reporting outcomes on totally endoscopic mitral valve surgery. "Totally endoscopic" was defined as incisions less than 3cm and the avoidance of rib spreading. The primary outcome was 30-day mortality and secondary endpoints included postoperative myocardial infarction (MI), stroke, early reoperation, wound infection, renal failure, and prolonged ventilation. Perioperative patient characteristics were also recorded and analyzed. Thirty-three studies (6031 patients) were included in our meta-analysis. The 30-day mortality rate was 0.33%, p=0.88. The most frequent complications were early reoperation (2.12%, p=0.44) and prolonged ventilation (1.46% p=<0.01). Rates of MI, stroke, and renal failure were each less than 1%. Patient characteristics including age, body mass index (BMI), and ejection fractions were also analyzed. We propose a formal definition of TEMVS, which is performed through incisions less than 3cm and without rib spreading. Thirty-day mortality and other adverse sequelae of TEMVS are uncommon.


New strategy and easy fabrication of solid-state supercapacitor based on polypyrrole and nitrile rubber.
Solid state redox supercapacitors were fabricated using a solid polymer electrolyte, nitrile butadiene rubber (NBR)-KCI and chemically deposited polypyrrole (PPy) as the conducting polymer electrodes on both surfaces of a NBR film. The optimal conditions for the preparation of the PPy/NBR electrode were confirmed as functions of the uptake of pyrrole monomer into the NBR matrix as well as the immersion time in an oxidant solution. The morphology of the PPy-NBR-KCI capacitor was observed using scanning electron microscopy. The performance of the capacitors was characterized using a galvanostatic charge-discharge technique.


Erianin inhibits human lung cancer cell growth via PI3K/Akt/mTOR pathway in vitro and in vivo.
Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1 day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.


Application of microwave irradiation for the removal of polychlorinated biphenyls from siloxane transformer and hydrocarbon engine oils.
The removal of polychlorinated biphenyls (PCBs) both from siloxane transformer oil and hydrocarbon engine oil was investigated through the application of microwave (MW) irradiation and a reaction system based on polyethyleneglycol (PEG) and potassium hydroxide. The influence of the main reaction parameters (MW irradiation time, molecular weight of PEG, amount of added reactants and temperature) on the dechlorination behavior was studied. Promising performances were reached, allowing about 50% of dechlorination under the best experimental conditions, together time and energy saving compared to conventional heating systems. Moreover, an interesting dechlorination degree (up to 32%) was achieved for siloxane transformer oil when MW irradiation was employed as the unique driving force. To the best of our knowledge, this is the first time in which MW irradiation is tested as the single driving force for the dechlorination of these two types of PCB-contaminated oils.


Novel decision tree algorithms for the treatment planning of compromised teeth.
In clinical practice, dentists are faced with the dilemma of whether to treat, maintain, or extract a tooth. Of primary importance are the patient's desires and the restorability and periodontal condition of the tooth/teeth in question. Too often, clinicians extract teeth when endodontic therapy, crown-lengthening surgery, forced orthodontic eruption, or regenerative therapy can be used with predictable results. In addition, many clinicians do not consider the use of questionable teeth as provisional or transitional abutments. The aim of this article is to present a novel decision tree approach that will address the clinical deductive reasoning, based on the scientific literature and exemplified by selective case presentations, that may help clinicians make the right decision. Innovative decision tree algorithms will be proposed that consider endodontic, restorative, and periodontal assessments to improve and possibly eliminate erroneous decision making. Decision-based algorithms are dynamic and must be continually updated in accordance with new evidence-based studies.


The origin of carbon isotope vital effects in coccolith calcite.
Calcite microfossils are widely used to study climate and oceanography in Earth's geological past. Coccoliths, readily preserved calcite plates produced by a group of single-celled surface-ocean dwelling algae called coccolithophores, have formed a significant fraction of marine sediments since the Late Triassic. However, unlike the shells of foraminifera, their zooplankton counterparts, coccoliths remain underused in palaeo-reconstructions. Precipitated in an intracellular chemical and isotopic microenvironment, coccolith calcite exhibits large and enigmatic departures from the isotopic composition of abiogenic calcite, known as vital effects. Here we show that the calcification to carbon fixation ratio determines whether coccolith calcite is isotopically heavier or lighter than abiogenic calcite, and that the size of the deviation is determined by the degree of carbon utilization. We discuss the theoretical potential for, and current limitations of, coccolith-based CO2 paleobarometry, that may eventually facilitate use of the ubiquitous and geologically extensive sedimentary archive.


Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status.
Targeted molecular therapy is an effective anticancer strategy. Anti-EGFR monoclonal antibodies such as cetuximab (CTX) have been approved for the treatment of various malignancies, including colorectal cancer (CRC) with wild-type KRAS. However, their efficacy in patients with KRAS mutations has not been established. Therefore, we investigated whether CTX treatment was effective as a single agent or in combination with zoledronic acid (ZOL) in human CRC cell lines with different KRAS status. CRC cell lines SW48 (wild-type KRAS) and LS174T (mutant KRAS) were treated with ZOL, CTX and a combination of both drugs. Cytotoxicity was measured using the MTT assay. Changes in the levels of intracellular signaling proteins were evaluated using western blot analysis. Finally, we evaluated the efficacy of the combination treatment in an in vivo xenograft model. We observed that ZOL apparently inhibited growth in both cell lines, whereas CTX showed little effect. ZOL also increased the levels of unprenylated RAS. Combined ZOL and CTX treatment was synergistic in both cell lines and was associated with inhibition of the RAS-MAPK and AKT-mTOR signaling pathways. Furthermore, the combination treatment was more effective in suppressing the growth of xenografts derived from both SW48 and LS174T cells; this effect was associated with increased apoptosis. These results demonstrate that ZOL inhibits the growth of colon cancer cells regardless of KRAS status, and combination therapy using ZOL and CTX enhances this growth suppression. These findings suggest a novel strategy for the treatment of CRC independent of KRAS mutational status.


Coordinated assembly of multisubunit proteins: oligomerization of bacterial enterotoxins in vivo and in vitro.
In this paper we study the assembly, in vivo and in vitro, of a family of hexameric, heat-labile enterotoxins produced by diarrheagenic bacteria. The toxins, which consist of an A subunit and five B subunits, are assembled by a highly coordinated process that ensures secretion of the holotoxin complex. We show that (i) oxidation of cysteine residues in the B subunits is a prerequisite step for in vivo formation of B-subunit pentamers, (ii) reduction of dissociated B subunits in vitro abolishes their ability to reassemble, (iii) the kinetics of B-pentamer assembly in vivo can be mimicked under defined conditions in vitro, (iv) A subunits cannot associate with fully assembled B pentamers in vitro, and (v) A subunits cause an approximately 3-fold acceleration in the rate of B-subunit pentamerization in vivo, implying that A subunits play a coordinating role in the pathway of holotoxin assembly. The last finding is likely to be of general significance, since it provides a mechanism for preferentially excluding or favoring certain intermediates in the assembly of multisubunit proteins.


Factors influencing the toxicity of Headline® fungicides to terrestrial stage toads.
Amphibians are susceptible to exposure from contaminants via multiple pathways. Pyraclostrobin fungicides have been shown to be toxic to terrestrial amphibians at environmentally relevant concentrations; however, these studies did not account for factors that may influence exposure and effects, such as fungicide formulation, age of the individual, exposure route, and physiological state of the individual. We examined Headline® and Headline AMP® fungicide toxicity to adult Anaxyrus cognatus and Anaxyrus woodhousii by direct overspray, as well as acute toxicity of Headline AMP to juvenile A. cognatus through direct overspray, previously exposed soils, and diet. We also assessed effects of hydration state on fungicide toxicity in juvenile A. cognatus and sublethal effects of fungicide exposure on prey-orientation ability of juvenile A. cognatus. Neither formulation of Headline caused mortality of adult A. cognatus and A. woodhousii at up to 5 times the maximum label rate in North American corn (1052 and 879 mL formulation/ha for Headline AMP and Headline fungicides, respectively, corresponding to 1.52 and 2.2 μg pyraclostrobin/cm2 , respectively). Exposures of juvenile A. cognatus to Headline AMP via direct overspray and previously exposed soils (2 types) resulted in median lethal rate (LR50) values of 2.4, 3.34, and 3.61 μg pyraclostrobin/cm2 , respectively. Dietary Headline AMP exposure was not toxic, prey-orientations were not influenced by exposure, and effects were similar between dehydrated and hydrated treatments (LR50 = 2.4 and 2.3 μg pyraclostrobin/cm2 , respectively). These results, combined with exposure concentrations reported in previous studies, suggest that risk of acute mortality for amphibians in terrestrial environments is low and is dictated by body size and site-specific factors influencing exposure. Environ Toxicol Chem 2017;36:2679-2688. © 2017 SETAC.


The effect of monocular depth cues on the detection of moving objects by moving observers.
An observer moving through the world must be able to identify and locate moving objects in the scene. In principle, one could accomplish this task by detecting object images moving at a different angle or speed than the images of other items in the optic flow field. While angle of motion provides an unambiguous cue that an object is moving relative to other items in the scene, a difference in speed could be due to a difference in the depth of the objects and thus is an ambiguous cue. We tested whether the addition of information about the distance of objects from the observer, in the form of monocular depth cues, aided detection of moving objects. We found that thresholds for detection of object motion decreased as we increased the number of depth cues available to the observer.


Ultrasensitive, Biocompatible, Self-Calibrating, Multiparametric Temperature Sensors.
Core-shell quantum dots serve as self-calibrating, ultrasensitive, multiparametric, near-infrared, and biocompatible temperature sensors. They allow temperature measurement with nanometer accuracy in the range 150-373 K, the broadest ever recorded for a nanothermometer, with sensitivities among the highest ever reported, which makes them essentially unique in the panorama of biocompatible nanothermometers with potential for in vivo biological thermal imaging and/or thermoablative therapy.


Conservation of the dimeric unit of H2A and H2B histones during the replication cycle.
The behavior of H2A and H2B histones during the replication cycle has been investigated. H2A-H2B dimer fractions obtained from MH-134SC cells labeled with suitable precursors were fractionated by rate zonal centrifugation in sucrose gradients containing 2 M NaCl. Labeling for one round of replication cycle with an amino acid mixture enriched with dense isotopes and [3H]lysine as a radioactive marker yielded a distinct peak of dense dimer that sedimented faster than the normal dimer. Similar density labeling of cells did not cause measurable alteration in the sedimentation profile of the preexisting normal dimer marked with [14C]lysine. The data suggest conservation of the bulk of the dimeric unit during the replication cycle. Biological significance of the dimeric behavior of H2A and H2B is discussed in favor of the partially conservative model of histone octamer assembly.


Eye safety for scanning laser projection systems.
In the growing field of pico-projectors, laser-based scanning systems may be advantageous over DLP- or LCoS-based imagers due to their potential for miniaturization, enhanced optical efficiency and cost reduction. The high energy density of a combined laser beam can, however, be hazardous to the human eye. Laser projection systems must therefore be identified with the laser class, depending on their maximum optical output power. This power limits the brightness of the displayed image, which is of particular interest for mobile applications. Various approaches to classifying laser devices by their wavelength and output power are described within the standards for laser safety. It is found that actual safety regulations cannot be directly applied to scanning systems. A detailed analysis of the optical conditions in terms of a two-dimensional extended light source is appropriate for the consideration of laser scanner devices. In this article, alternative ways of applying laser standards for scanning systems are discussed. The dependencies of maximum luminous flux from scanning system parameters are reviewed. It is shown that the evaluation of retinal light exposure in terms of existing laser regulations leads to an overestimation of the hazardous potential. Advanced investigations are proposed to support the definition of suitable criteria for the classification of laser scanning projectors.


Insights Into the Cardiomodulatory Effects of Sex Hormones: Implications in Transgender Care.
Transgender individuals that undergo gender-affirming hormone therapy may experience discrimination in the health care setting with a lack of access to medical personnel competent in transgender medicine. Recent evidence suggests that gender-affirming hormone therapy is associated with an increased risk of cardiovascular diseases and cardiovascular risk factors. A recent statement from the American Heart Association reinforces the importance of cardiovascular-focused clinical management and the necessity for more research into the impact of gender-affirming hormone therapy. With this in mind, this review will highlight the known cardiovascular risk factors associated with gender-affirming hormone therapy and identify potential molecular mechanisms determined from the limited animal studies that explore the role of cross-sex steroids on cardiovascular risk. The lack of data in this understudied population requires future clinical and basic research studies to inform and educate clinicians and their transgender patient population to promote precision medicine for their care to improve their quality of life.


Health Policy Development During COVID-19 in Saudi Arabia: Mixed Methods Analysis.
Healthcare systems are increasingly required to utilize effective approaches, apply evidence-based practice, and consequently sustain successful strategic management. Document analysis provides insights into the effective management tools applied by agencies to respond to crises. This article provides a practical exploration of how the Saudi health authority applied effective measures to eventually reduce the administrative and clinical consequences while managing the COVID-19 pandemic. The conceptual descriptive framework was based on health policy triangle of Walt and Gilson. Official reports and supporting documents issued by the Saudi government toward COVID-19 were operationally analyzed. Moreover, five healthcare professional experts were invited in a semistructured interview to assess the strategic steps that have been utilized to minimize the health risk by conducting a healthcare risk analysis. Various documents showed that two major entities were responsible for managing regulations and medications of COVID-19 in addition to six other entities that were partially involved. Although each entity was approved to work independently, their efforts were cohesively associated with each other. Most documents were well-applied on personal, social, organizational, and national strata. However, it is unclear how lessons identified became affirmative, while the collaboration remains vague, especially under the emergence of a new entity such as the Public Health Authority. Healthcare professional experts also positively supported the effectiveness of such policies to confront COVID-19 through the following three domains: health guidelines, utilizing simulation (telehealth/telecommunication) services, and ensuring continuity of services.


Tc-99m Depreotide SPECT/CT depicts myocardial involvement in a case of thrombotic thrombocytopenic purpura.
We report a case of thrombotic thrombocytopenic purpura (TTP) with cardiac involvement, imaged with Tc-99m depreotide. A 56-year-old man presented with fever, hematuria, and chest pain. Laboratory findings (angiopathic hemolytic anemia, thrombocytopenia, and uremia) were suggestive of TTP. Cardiac enzymes were elevated and diffuse left ventricular hypokinesis was demonstrated by echocardiography. Serum rheumatologic and virologic analysis were negative. A Tc-99m depreotide SPECT/CT study showed diffuse uptake in the myocardium, indicating inflammatory reaction to thrombotic/hemorrhagic myocardial damage. We suggest that Tc-99m depreotide imaging may reveal myocardial involvement in TTP; this could prompt further investigation for potential applications in myocarditis of other etiologies.


Use of the internet to enhance infectious disease surveillance and outbreak investigation.
Modernization of electronic communication systems to facilitate infectious disease surveillance and outbreak investigation became a priority after the 2001 anthrax attacks. However, the extent to which communicable disease investigators are using web-based information resources, e-mail notifications, or secure information exchange systems to facilitate surveillance is unknown. To address this question, we conducted a survey in 2004 of state and local communicable disease investigators responsible for infectious disease surveillance and outbreak investigation in three states. The majority (70.7%) of the 297 respondents accessed the Internet for information regarding infectious disease surveillance and outbreaks at least weekly. Most (74%) respondents who searched for information from the Centers for Disease Control and Prevention (CDC) website reported that they found what they were looking for 75-100% of the time, compared with 54% who found the information from their state health department websites 75-100% of the time. One-third of respondents read e-mail notifications regarding outbreaks under investigation in their state less frequently than monthly; 34% of those enrolled in CDC's Epidemic Information Exchange (Epi-X) read e-mail notifications of new reports less frequently than monthly. Forty-seven (18%) respondents read ProMED-mail at least monthly, while 46% indicated they had never consulted MEDLINE/PubMed. Some progress has been made in use of the Internet to facilitate communication in infectious disease surveillance and outbreak investigation. Addressing barriers to access and usability of new information systems in conjunction with training and technical support could enhance infectious disease surveillance and timely investigation of outbreaks and bioterrorism events.