Does the Electronic Structure of Möbius Annulenes Follow Heilbronner's Ideas?
It is shown, on the example of the monocyclic cyclononatetraenyl cation, C 9 H 9 + , that the fully-variational optimization of modern ab initio wavefunctions based on spin-coupled generalized valence bond (SCGVB) theory vindicates, in a surprising level of detail, essential features of Heilbronner's ideas for the electronic structure of Möbius annulenes such as the arrangement of overlapping carbon 2p atomic orbitals along a Möbius strip, leading to a phase inversion between the first and last orbitals. In the SCGVB description, the aromaticity of this Möbius system with eight π electrons follows from the extensive resonance between VB structures.


Oculopharyngeal and distal myopathy: a case study from Papua New Guinea.
Distal limb myopathy with onset at 30 years, followed by the development of progressive ptosis, external ophthalmoplegia, and pharyngeal myopathy was observed in a 37-year-old Melanesian man from the Gulf Province of Papua New Guinea. Ptosis and external ophthalmoplegia without apparent distal muscle involvement or dysphagia with onset at 35 and 25 years of age, respectively, were noted in the patient's 44- and 27-year-old sisters. Autosomal recessive inheritance appears to be likely in this family. This myopathic syndrome has not previously been reported in Melanesians.


A matched-pair comparison of two cochlear implant systems.
To compare the overall performance of two implant systems based on audiologic outcome, tinnitus handicap, and quality of life using objective and subjective measures. Retrospective cohort study. Sunnybrook & Women's College Health Science Centre. Two matched groups, with 24 Nucleus 22 SPEAK (Advanced Bionics, Symlar, CA) and 24 Clarion CIS (Cochlear Corporation, Sydney, Australia), were selected. Patients were administered survey forms to evaluate subjective tinnitus and dizziness symptomatology, as well as a 27-item tinnitus handicap questionnaire. Both groups were administered survey forms to assess the frequency of implant use, the subjective benefit derived, and the perceived impact on quality of life. The 36-Item Short-Form (SF-36) Health Survey was administered as a measure of quality of life at 6 months postimplant. Standardized open-set speech recognition parameters were evaluated at 24 months postimplant. Vestibular function was determined by pre-and postimplant electronystagmography with caloric testing. The first author was blinded to implant type during data collection and analysis Cochlear implantation yielded a significant 22% reduction in overall tinnitus handicap (p < .05). There was a 27% reduction in vestibular function that failed to show statistical significance (p = .78). There was no significant reduction in vestibular function postimplant in either group. The average open-set speech perception responses at 24 months postimplant were monosyllabic word recognition 45%, phoneme recognition 65%, and sentence recognition 86.5%. There was no significant difference with respect to implant type. Overall, 76% of implantees reported satisfaction with the amount of subjective benefit they received from their implants. Furthermore, 96% reported an overall positive impact on quality of life. Overall, there was no significant difference between the two multichannel devices studied using the present software and hardware configurations.


Rice expressing lactoferrin and lysozyme has antibiotic-like properties when fed to chicks.
Two experiments were conducted to determine whether rice that has been genetically produced to express human lactoferrin (LF) or lysozyme (LZ) protects the intestinal tract similarly to subtherapeutic antibiotics (bacitracin + roxarsone; Antibiotics). Experiment 1 compared 10 corn-soy diets containing 20% of various proportions of LF, LZ or conventional rice (CONV). Chicks fed 5% LF + 10% LZ + 5% CONV had significantly better feed efficiency and thinner lamina propria in the duodenum than those fed 20% CONV. Experiment 2 compared five corn-soy diets containing experimental rice combinations totaling 15% rice. Chicks fed 10% LZ + 5% CONV or 5% LF + 10% LZ had significantly lower feed intake and significantly better feed efficiency than those fed 15% CONV. Chicks fed 10% LZ + 5% CONV, 5% LF + 10% LZ or Antibiotics had significantly greater villous height in the duodenum compared with chicks fed 15% CONV. The lamina propria of the ileum was thinner and contained fewer leukocytes in chicks fed 10% LZ + 5% CONV or Antibiotics compared with those fed 15% CONV. The results from these experiments demonstrate a potential of genetically produced LF and LZ rice to be used as a substitute for antibiotics in broiler diets.


Ischemic preconditioning modulates ROS to confer protection in liver ischemia and reperfusion.
Ischemia reperfusion (IR) injury is a significant cause of morbidity and mortality in liver transplantation. When oxygen is reintroduced to the liver graft it initiates a cascade of molecular reactions leading to the release of reactive oxygen species (ROS) and pro-inflammatory cytokines. These soluble mediators propagate a sterile immune response to cause significant tissue damage. Ischemic preconditioning (IPC) is one method that reduces hepatocellular injury by altering the immune response and inhibiting the production of ROS. Studies quantifying the effects of IPC in humans have demonstrated an improved liver enzyme panel in patients receiving grafts pretreated with IPC as compared to patients receiving the standard of care. In our review, we explore current literature in the field in order to describe the mechanism through which IPC regulates the production of ROS and improves IR injury.


Estrogen replacement reduces PGHS-2-dependent vasoconstriction in the aged rat.
The reduction in estrogen in postmenopausal women contributes to an increase in vascular dysfunction. Models of aging have shown that this is due, in part, to increased prostaglandin H synthase (PGHS)-dependent vasoconstriction. We showed previously that inducible PGHS-2-dependent vasoconstriction is increased with aging. In the present study, we hypothesized that estrogen suppresses PGHS-2-dependent constriction in the aged rat. Isolated mesenteric arteries from placebo- or estrogen-treated, ovariectomized aged (24 mo) Fisher rats were assessed for endothelium-dependent relaxation in the absence or presence of PGHS inhibitors. PGHS inhibition (meclofenamate, 1 micromol/l) enhanced methacholine-induced relaxation only in the placebo group. Specific PGHS-2 inhibition (NS-398, 10 micromol/l) increased arterial relaxation to a greater extent than PGHS-1 inhibition (valeryl salicylate, 3 mmol/l). Estrogen prevented the PGHS-dependent constrictor effect but did not enhance nitric oxide-dependent relaxation in this model. PGHS-1 and endothelial nitric oxide synthase were not altered by estrogen, whereas PGHS-2 expression was decreased in the estrogen-replaced rats (P < 0.05). In summary, estrogen replacement improved vasodilation in aged rats by decreasing PGHS-dependent constriction.


Bariatric surgery and birth defects: A systematic literature review.
Bariatric procedures are on the rise. The risk of birth defects in pregnancies following such procedures may be increased (eg, due to nutrient deficiencies) or decreased (eg, due to decreased maternal body mass index, BMI). We conducted a systematic literature review of the association between bariatric surgery and birth defects using Ovid MEDLINE and PubMed (1946-2017). Information was abstracted on study design, exposures, outcomes, covariates and estimates of association. Fifteen studies met our inclusion criteria: 14 evaluated the outcome of any birth defect, and one evaluated neural tube defects. Estimates of association between bariatric surgery and birth defects were available for nine studies and ranged from 0.6 to 1.9 (all 95% confidence intervals included 1.0). When studies were stratified by surgery type, there was no obvious pattern of association. When stratified by the approach used to account for BMI, positive associations were observed in studies that did not account for maternal prepregnancy BMI or used women with normal BMI as the reference group (range: 1.3-1.9). Estimates from studies that either matched or adjusted for prepregnancy BMI were closer to the null (range: 1.1-1.2) and studies that compared to morbidly obese women reported protective associations (range: 0.6-0.7). Studies of the association between bariatric surgery and birth defects vary with respect to the surgical procedures included, birth defects ascertainment methods and approaches used to account for maternal BMI. Consequently, it is not possible to draw a conclusion regarding the association between bariatric surgery and birth defects. Additional studies are warranted.


Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice.
Caveolins are important components of caveolae, which have been implicated in vesicular trafficking and signal transduction. To investigate the in vivo significance of Caveolins in mammals, we generated mice deficient in the caveolin-1 (cav-1) gene and have shown that, in the absence of Cav-1, no caveolae structures were observed in several nonmuscle cell types. Although cav-1(-/-) mice are viable, histological examination and echocardiography identified a spectrum of characteristics of dilated cardiomyopathy in the left ventricular chamber of the cav-1-deficient hearts, including an enlarged ventricular chamber diameter, thin posterior wall, and decreased contractility. These animals also have marked right ventricular hypertrophy, suggesting a chronic increase in pulmonary artery pressure. Direct measurement of pulmonary artery pressure and histological analysis revealed that the cav-1(-/-) mice exhibit pulmonary hypertension, which may contribute to the right ventricle hypertrophy. In addition, the loss of Cav-1 leads to a dramatic increase in systemic NO levels. Our studies provided in vivo evidence that cav-1 is essential for the control of systemic NO levels and normal cardiopulmonary function.


Contextual and individual factors associated with public dental services utilisation in Brazil: A multilevel analysis.
This study verified the association between contextual and individual factors and public dental services utilisation in Brazil. The study was conducted based on a cross-sectional population-based household survey performed in Brazil (National Health Survey- 2019)). Data was collected between August 2019 and March 2020. Total sample included 43,167 individuals aged ≥15 years who had at least one dental appointment in the last 12 months before interview. Study outcome was 'public dental service utilisation', and Andersen's behavioral model was adopted for selecting independent variables. A multilevel analysis was performed using individual factors as first level and federation units as second level. The highest prevalence of public dental service utilisation on an individual level was observed among unable to read or write people (PR: 3.31; p<0.001), indigenous (PR: 1.40; p<0.001), black or brown (PR: 1.16; p<0.001), with per capita household income of up to U$124 (PR: 2.40; p<0.001), living in the rural area (PR: 1.28; p<0.001), and who self-rated oral health as regular (PR: 1.15; p<0.001) or very bad/bad (PR: 1.26; p<0.001). On the contextual level, highest PR of public dental service utilisation was observed among those living in federal units with increased oral health coverage in primary health care. Public dental service utilisation is associated with individual and contextual factors. These results can guide decision-making based on evidence from policymakers, demonstrating the potential for mitigating oral health inequalities and increasing service coverage in a public and universal health system.


Angle Class I malocclusion with anterior negative overjet.
This clinical case report describes the orthodontic treatment of an 8-year and 9-month old female patient with Angle Class I malocclusion, anterior crossbite and canine Class III relationship. Orthodontic treatment was carried out in two stages. The first one was orthopedic, while the second one included the use of a fixed appliance and the need for space gain for reshaping of maxillary lateral incisors. The two-stage treatment combined with multidisciplinary Restorative Cosmetic Dentistry allowed excellent esthetic and functional outcomes to be achieved. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as a requirement for the title of certified by the BBO.


Spectrofluorimetry at zero angle: determination of salicylic acid in an acetylsalicylic acid pharmaceutical formulation.
In this work, a solid-state spectrofluorimetric method for drug assays was developed. In particular, we report the determination of salicylic acid (SA), as a hydrolysis product, in solid pharmaceutical formulations containing acetylsalicylic acid (ASA). Recently, we described a sensitive and accurate fluorescence method that provided, through a mathematical application, the simultaneous determination of ASA and SA. By means of the spectrofluorimetric method reported herein it was possible to carry out the SA determination, without any mathematical calculation and with a sensitivity 100 times that of our previous method. The intra- and inter-day reproducibility of the spectrofluorimetric method, expressed as the relative standard deviation, ranged from 0.1 to 0.3%. The present method requires a fluorescence apparatus with the excitation and detection systems in-line (zero angle). The detection system was not sensitive to the excitation wavelength, but was highly sensitive to emission wavelengths from 350 to 800 nm. The results obtained were compared with those of our previous spectrofluorimetric method, together with those of a high-performance liquid chromatography method and a US Pharmacopeia method. The sensitivity of the method was of the order of 10(-8) g.


Spontaneous closure of a perforation-induced coronary artery pseudoaneurysm.
We describe an unusual case of a coronary perforation presenting as a large pseudoaneurysm. An elderly woman who had undergone percutaneous coronary intervention several months earlier presented with shortness of breath. Cardiac catheterization revealed a large pseudoaneurysm arising from the proximal circumflex artery. At follow-up angiography a few days later, the pseudoaneurysm had spontaneously closed. In the discussion, we describe the incidence and treatment of this rare complication.


Regulation of collagenase gene expression in synovial cells.
The metalloproteinase collagenase that is synthesized and secreted by synovial cells is responsible for the large amount of connective tissue destruction seen in rheumatoid arthritis. We have used a model system of cultured rabbit synovial fibroblasts to better understand mechanisms controlling both the induction and suppression of collagenase synthesis. Induction of collagenase requires an increase in collagenase mRNA and concomitantly, suppression of collagenase synthesis by retinoids and glucocorticoids is accompanied by a decrease in collagenase mRNA. Another metalloproteinase, activator, which is responsible for the activation of latent procollagenase and which has gelatinolytic ability, is coordinately regulated with collagenase. We conclude that there may exist a family of metalloproteinases that is important in the modulation of connective tissues and that is coordinately regulated at the level of mRNA.


Chronic changes in rabbit retro-patellar cartilage and subchondral bone after blunt impact loading of the patellofemoral joint.
Animal models of acute joint injury are useful for study of changes in joint tissues that may eventually lead to degradative disease. Our laboratory has developed a joint trauma model using a single blunt impact to the patellofemoral joint of rabbits and documented softening of retro-patellar cartilage and thickening of its underlying bone out to 12 months post-trauma. In the present study, we examined changes in these joint tissues out to 36 months post-impact. Forty-nine Flemish giant rabbits were impacted on the right patellofemoral joint and sacrificed at one of six times: 0, 4.5, 7.5, 12, 24, and 36 months post-impact. A 30% reduction in the compressive modulus of traumatized retro-patellar cartilage occurred at 4.5 months versus the contralateral, non-impacted limb and remained at this reduced level out to 36 months. The fluid permeability of traumatized cartilage also increased over time from baseline and versus the non-impacted limb. Tissue thickness increased slightly at 4.5 months and then decreased over time to a 45% difference from baseline at 36 months post-trauma. While impacted cartilage revealed a significantly greater length of surface fissuring than contralateral, non-impacted cartilage, no time-dependent changes were evident in this study. Moreover, the number and depth of these impact surface lesions did not change as a function of time. Finally, the histological analyses indicated that the thickness of underlying subchondral bone increased over time from baseline and versus that in the non-impacted limb. This long-term study suggested an association between a decrease in the characteristic time constant of traumatized cartilage and thickening of the underlying subchondral bone. Any potential cause and effect relationship, however, must be investigated in future studies.


Contrasting Nutrient Mitigation and Denitrification Potential of Agricultural Drainage Environments with Different Emergent Aquatic Macrophytes.
Remediation of excess nitrogen (N) in agricultural runoff can be enhanced by establishing wetland vegetation, but the role of denitrification in N removal is not well understood in drainage ditches. We quantified differences in N retention during experimental runoff events followed by stagnant periods in mesocosms planted in three different vegetation treatments: unvegetated, cutgrass [ (L.) Sw.], and common cattail ( L.). We also quantified denitrification rates using membrane inlet mass spectrometry from intact cores extracted from each mesocosm treatment. All treatments retained 60% or more of NO-N loads during the 6-h experimental runoff event, but mesocosms planted with cutgrass had significantly higher (68%) retention than the cattail (60%) or unvegetated (61%) treatments. After the runoff event, mesocosms planted in cattail reduced NO-N concentrations by >95% within 24 h and cutgrass achieved similar reductions within 48 h, whereas reductions in the unvegetated mesocosms were significantly less (65%). Cores from cutgrass mesocosms had significantly higher average denitrification rates (5.93 mg m h), accounting for as much as 56% of the immobilized NO-N within 48 h, whereas denitrification rates were minimal in cores from the unvegetated (-0.19 mg m h) and cattail (0.2 mg m h) mesocosms. Our findings have implications for mitigating excess NO-N in agricultural runoff. While vegetated treatments removed excess NO-N from the water column at similar and significantly higher rates than unvegetated treatments, the high denitrification rates observed for cutgrass highlight the potential for permanent removal of excess N from agricultural runoff in vegetated ditches and wetlands.


Parasite suppression of the oxidations of eumelanin precursors in Drosophila melanogaster.
In insects, eukaryotic endoparasites encounter a series of innate immune effector responses mediated in large part by circulating blood cells (hemocytes) that rapidly form multilayer capsules around foreign organisms. Critical components of the encapsulation response are chemical and enzyme-catalyzed oxidations involving phenolic and catecholic substrates that lead to synthesis of eumelanin. These responses are initiated immediately upon infection and are very site-specific, provoking no undesirable systemic responses in the host. In this study, we were interested to learn if the principal oxidation pathways leading to the synthesis of eumelanin in larvae of Drosophila melanogaster were targets for inhibition by immune suppressive factors (ISF) derived from a virulent strain of the endoparasitic wasp Leptopilina boulardi. Comparative in vitro assays monitored by sensitive electrochemical detection methods showed that ISF derived from female reproductive tissues significantly diminished the oxidations of the two diphenol eumelanin precursors, dopamine and 5,6-dihydroxyindole (DHI). The oxidations of the monophenol tyrosine, and two other related diphenols, dopa and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), were not significantly inhibited by ISF. The data suggest that melanogenesis represents at least one of the host responses suppressed by L. boulardi ISF, and that the oxidation pathways selectively targeted for inhibition are those synthesizing decarboxylated pigment precursors derived from DHI. These observations, together with previous reports of adverse effects of ISF on the ability of hemocytes to adhere to foreign surfaces, suggest a multifaceted approach by the parasitoid to circumvent the innate immune response of D. melanogaster.


[Physico-chemical characterization of human seminal plasma specific antigen p30].
Human seminal plasma specific antigen p30, which has been characterized by other authors under the name of prostate-specific antigen or gamma-seminoprotein, has been purified. This communication describes the physico-chemical characterization of p30 demonstrated by various SDS-polyacrylamide gel electrophoresis and isoelectrofocusing as well as amino acid analysis. The results showed that the molecular weight of p30 was 33 kd and its isoelectric point was around pH 6.9. Its amino acid composition was similar to that of prostate-specific antigen. It is concluded that p30 purified by our laboratory and prostate-specific antigen named by Wang are the identical one of isomers.


Does hepato-splanchnic VO2/DO2 dependency exist in critically ill septic patients?
Since the gradient between the mixed venous and hepatic vein oxygen saturation (DSO2) is often increased in septic patients, we suspected these patients may have an imbalance between oxygen supply and demand in the hepato-splanchnic area. In 42 septic patients, hepato-splanchnic blood flow was determined by the indocyanine green clearance method with hepatic vein catheterization. The relationships between hepato-splanchnic oxygen delivery (DO2spla) and consumption (VO2spla) were analyzed during an increase in blood flow induced by a dobutamine infusion at doses up to 10 microg/kg x min. In 14 patients, positive end-expiratory pressure (PEEP) was also increased up to 20 cm H2O. The patients were separated according to their DSO2 (Group I: DSO2 < 10%, n = 13; and Group II: DSO2 > 10%, n = 29). Although DO2spla increased similarly in both groups, VO2spla only increased in Group II (from 45+/-22 to 59+/-39 ml/min x M2, p < 0.01). The slope of the VO2spla/DO2spla relationship was higher in Group II than in Group I (31.2+/-16.7 versus 10.4+/-5.1%, p < 0.001) and was similar during dobutamine and PEEP (21.9+/-14.2 versus 21.9+/-14.0%, p = NS). In conclusion, VO2spla increased only in septic patients with an increased DSO2 indicating splanchnic dysoxia. The similar slope observed with dobutamine and PEEP suggests that a thermogenic effect was unlikely.


Curcumin as a potential treatment for Alzheimer's disease: a study of the effects of curcumin on hippocampal expression of glial fibrillary acidic protein.
Curcumin, an agent traditionally utilized for its preventative action against tumorigenesis, oxidation, inflammation, apoptosis and hyperlipemia, has also been used in the treatment of Alzheimer's disease (AD). Recent advances in the study of AD have revealed astrocytes (AS) as being key factors in the early pathophysiological changes in AD. Glial fibrillary acidic protein (GFAP), a marker specific to AS, is markedly more manifest during morphological modifications and neural degeneration signature during the onset of AD. Several studies investigating the functionality of curcumin have shown that it not only inhibits amyloid sedimentation but also accelerates the disaggregation of amyloid plaque. Thus, we are interested in the relationship between curcumin and spatial memory in AD. In this study, we intend to investigate the effects of curcumin in amyloid-β (Aβ(1-40)) induced AD rat models on both the behavioral and molecular levels, that is to say, on their spatial memory and on the expression of GFAP in their hippocampi. Our results were statistically significant, showing that the spatial memory of AD rats improved following curcumin treatment (p < 0.05), and that the expression of GFAP mRNA and the number of GFAP positive cells in the curcumin treated rats was decreased relative to the AD group rats (p < 0.05). Furthermore, the expression level of GFAP mRNA in hippocampal AS in the AD rats significantly increased when compared with that in the sham control (p < 0.05). Taken together, these results suggest that curcumin improves the spatial memory disorders (such disorders being symptomatic of AD) in Aβ(1-40)-induced rats by down regulating GFAP expression and suppressing AS activity.


An inducible 70 kDa-class heat shock protein is constitutively expressed during early development and diapause in the annual killifish Austrofundulus limnaeus.
The annual killifish Austrofundulus limnaeus inhabits ephemeral ponds in regions of northern South America, where they survive the periodic drying of their habitat as diapausing embryos. These diapausing embryos are highly resistant to a number of environmental insults such as high temperature, dehydration, anoxia, and increased salinity. Molecular chaperones are known to play a role in stabilizing protein structure and function during events of cellular stress. Relative levels of heat shock protein (Hsp)70 were measured in developing and diapausing embryos of A. limnaeus using quantitative Western blots. An inducible or embryo-specific form of Hsp70 is expressed during embryonic development in A. limnaeus and is elevated during diapause II in this species. Constitutive expression of Hsp70 during development may afford these embryos protection from environmental stresses during development more quickly than relying on the induction of a classic heat shock response.


The emotional shape of our moral life: anger-related emotions and mutualistic anthropology.
The evolutionary hypothesis advanced by Baumard et al. makes precise predictions on which emotions should play the main role in our moral lives: morality should be more closely linked to "avoidance" emotions (like contempt and disgust) than to "punitive" emotions (like anger). Here, we argue that these predictions run contrary to most psychological evidence.


Application of magnetic resonance virtual endoscopy as a presurgical procedure before sialoendoscopy.
The objectives of this study were to investigate the feasibility of clinical application of magnetic resonance (MR) virtual endoscopy as a presurgical procedure before sialoendoscopy and to evaluate its value in the diagnosis of obstructive salivary gland diseases and preoperative visualization of endoluminal views. This study presents our initial experience to use MR virtual endoscopy for the presurgical visualization of salivary duct lumen and ductal pathologies in comparison to the sialoendoscopy findings in a feasibility study. Six consecutive patients with suspected obstructive salivary gland diseases underwent MR sialography with a three-dimensional fast imaging using steady-state acquisition. The three-dimensional MR data were transferred to an independent workstation and were postprocessed with navigator software to generate three-dimensional reconstruction and virtual endoscopic images. The fly-through mode was used to imitate the sialoendoscopic exploratory procedure. Then the patients underwent sialoendoscopy and the endoscopic findings were compared with the preoperative virtual endoscopic images. The MR data acquisition and postprocessing protocol were feasible. The virtual endoscopy created clear endoluminal views of salivary duct and the ductal pathologies. The diagnoses were all confirmed by surgical sialoendoscopy. The virtual endoscopic images showed close resemblance to the sialoendoscopic findings. MR virtual endoscopy is an effective and noninvasive diagnostic method for evaluating the endoluminal anatomy and pathologies of the salivary duct. The clinical application of MR virtual endoscopy as a presurgical procedure before sialoendoscopy is a valuable and promising approach, which can provide surgeons useful morphologic and pathologic information.


Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA.
Infiltrating T lymphocytes are considered to play a major pathological role in skin lesions of cutaneous lupus erythematosus (CLE), a cutaneous autoimmune disease of unknown aetiology. Earlier histological studies revealed that the inflammatory infiltrate in CLE skin lesions is predominantly composed of T lymphocytes, with a slight predominance of CD4+ over CD8+ T cells, but failed to explain the development of scarring skin lesions, characteristic for chronic discoid lupus erythematosus (CDLE). Because recent investigations have highlighted the relevance of cytotoxic lymphocytes in autoimmune tissue destruction, we hypothesized that the scarring CDLE lesions might be caused by cytotoxic T lymphocytes. To analyse skin biopsies of 15 patients with CLE [10 female, five male; localized CDLE (lCDLE), n = 5; disseminated CDLE (dCDLE), n = 5, subacute CLE (SCLE), n = 5] and five control biopsies taken from healthy controls and to characterize the inflammatory infiltrate. Methods We used immunohistochemistry, including staining for the cytotoxic molecule granzyme B, the skin-homing molecule cutaneous lymphocyte antigen (CLA) and the protein MxA, which is specifically induced by type I interferons (IFNs). We found a strong coexpression of granzyme B and CLA on lesional lymphocytes of patients with scarring lCDLE and dCDLE, which was significantly enhanced when compared with nonscarring SCLE and healthy controls. The increased expression of granzyme B was closely associated with the lesional expression of the type I IFN-induced protein MxA. Our results provide evidence that type I IFNs and potentially autoreactive cytotoxic lymphocytes targeting adnexal structures are highly associated with scarring lupus erythematosus lesions and might be responsible for their scarring character.


Haemodialysis with charcoal haemoperfusion.
An activated charcoal haemoperfusion device containing 300 g acrylic hydrogel coated activated charcoal, was combined with haemodialysis, on six occasions in each of two patients, for a 2-hour portion of a routine 5-hour dialysis schedule. Blood pressure changes with combined treatment were minimised by using a low priming volume dialysis filter. Plasma clearance of both creatinine and urate were increased during the combined haemodialysis-haemoperfusion period. During the two hours of the combined treatment period in one patient creatinine removal amounted to 70% and urate removal to 50% of that obtained during a 5-hour haemodialysis. No significant additional urea or phosphate removal occurred. Changes in middle molecular weight substances with combined treatment were slightly greater than changes occurring with dialysis alone. Haemodialysis alone did not result in a terminal platelet fall, but combined treatment resulted in a terminal 20-30% platelet reduction, despite unchanged platelet counts at the end of the 2-hour haemoperfusion period. This preliminary study suggests that combined haemodialysis-haemoperfusion, is worthy of further scrutiny.


Retrieval of Embolized Amplatzer Patent Foramen Ovale Occlusion Device: Issues Related to Late Recognition.
Embolization of a percutaneous patent foramen ovale (PFO) closure device is a rare but serious complication. While early, periprocedural device embolization can normally be managed with snare and percutaneous retrieval, late embolization requires a different management strategy due to inability of the device to deform to allow passage into a large caliber sheath. We present a case of asymptomatic device embolization recognized six months following implantation and discuss the challenges encountered in successfully retrieving the device.


Correlation of pediatric outcomes data collection instrument with measures of active movement in children with brachial plexus birth palsy.
The purpose of this investigation was to characterize the range of Pediatric Outcomes Data Collection Instrument (PODCI) scores in children with brachial plexus birth palsy (BPBP) and determine its correlation with 3 published measures of active motion and function. One hundred fifty children with BPBP between the ages of 2 and 10 years were evaluated. Active upper-extremity motion was assessed using the modified Mallet Classification (MC), the Toronto Test score (TTS), and the Hospital for Sick Children Active Movement Scale. At the time of evaluation, patients and/or families were administered the age-appropriate PODCI questionnaire, and PODCI scores were compared with published normative data. Linear regression analysis was used to assess the correlation between MC, TTS, and Active Movement Scale as predictors of PODCI scores. Mean PODCI global function score in the BPBP patients was 82.4 (range, 35.1-100), significantly lower than the published value of 93.3 in healthy, age-matched norms (P < 0.01). The mean upper-extremity subscore was 70.8 versus 92.0 in healthy age-matched controls (P < 0.01). Sports/physical functioning scores averaged 81 points among BPBP patients compared with 90 points in healthy norms (P < 0.01). Mean mobility, comfort/pain, and happiness subscores were also significantly lower than normative values by 5, 7, and 4 points, respectively (P < 0.01). While significant correlations were observed between PODCI scores and all measures of active movement, the modified MC correlated most highly with PODCI global function scores in patients aged 2 to 5 years, whereas the TTSs best correlated with global function in patients aged 6 to 10 years. Brachial plexus birth palsy patients have lower global and upper-extremity function compared with their healthy, age-matched peers, as measured by the PODCI. Physician-derived measures of active movement correlate with the patient/parent-derived PODCI scores and may be used to predict global function, upper-extremity function, and sports/physical activity in children 2 to 10 years of age with BPBP.


A Systematic Review of the Use of Self-Assessment in Preclinical and Clinical Dental Education.
A desired outcome of dental and dental hygiene programs is the development of students' self-assessment skills. To that end, the Commission on Dental Accreditation states that "graduates must demonstrate the ability to self-assess." However, it is unclear that merely providing opportunity for self-assessment actually leads to the desired outcome. The aim of this study was to systematically review the literature on self-assessment in dental education. A search of English-language articles for the past 25 years (January 1, 1990, to June 30, 2015) was performed using MEDLINE Medical Subject Heading terms. Each abstract and/or article was validated for inclusion. The data collected included student classification, self-assessment environment, faculty assessment, training, faculty calibration, predictive value, and student perceptions. A qualitative analysis was also performed. From an initial list of 258 articles, 19 were selected for inclusion; exclusion criteria included studies that evaluated a non-preclinical or non-clinical exercise or whose subjects were not predoctoral dental or dental hygiene students. The results showed limited information regarding any kind of systematic training of students on how to perform a self-assessment. The majority of the studies also did not specify the impact of self-assessment on student performance. Self-assessment was primarily performed in the second year and in the preclinical environment. Students received feedback through a correlated faculty assessment in 73% of the studies, but 64% did not provide information regarding students' perceptions of self-assessment. There was a trend for students to be better self-assessors in studies in which a grade was connected to the process. In addition, there was a trend for better performing students to underrate themselves and for poorer performing students to overrate themselves and, overall, for students to score themselves higher than did their faculty evaluators. These findings suggest the need for greater attention to systematically teaching self-assessment in dental and dental hygiene curricula and for further research on the impact of self-assessment on desired outcomes.


New biarsenical ligands and tetracysteine motifs for protein labeling in vitro and in vivo: synthesis and biological applications.
We recently introduced a method (Griffin, B. A.; Adams, S. R.; Tsien, R. Y. Science 1998, 281, 269-272 and Griffin, B. A.; Adams, S. R.; Jones, J.; Tsien, R. Y. Methods Enzymol. 2000, 327, 565-578) for site-specific fluorescent labeling of recombinant proteins in living cells. The sequence Cys-Cys-Xaa-Xaa-Cys-Cys, where Xaa is an noncysteine amino acid, is genetically fused to or inserted within the protein, where it can be specifically recognized by a membrane-permeant fluorescein derivative with two As(III) substituents, FlAsH, which fluoresces only after the arsenics bind to the cysteine thiols. We now report kinetics and dissociation constants ( approximately 10(-11) M) for FlAsH binding to model tetracysteine peptides. Affinities in vitro and detection limits in living cells are optimized with Xaa-Xaa = Pro-Gly, suggesting that the preferred peptide conformation is a hairpin rather than the previously proposed alpha-helix. Many analogues of FlAsH have been synthesized, including ReAsH, a resorufin derivative excitable at 590 nm and fluorescing in the red. Analogous biarsenicals enable affinity chromatography, fluorescence anisotropy measurements, and electron-microscopic localization of tetracysteine-tagged proteins.


Double helical π-aggregate nanoarchitectonics for amplified circularly polarized luminescence.
The canonical double helical π-stacked array of base pairs within DNA interior has inspired the interest in supramolecular double helical architectures with advanced electronic, magnetic and optical functions. Here, we report a selective-recognized and chirality-matched co-assembly strategy for the fabrication of fluorescent π-amino acids into double helical π-aggregates, which show exceptional strong circularly polarized luminescence (CPL). The single crystal structure of the optimal combination of co-assemblies shows that the double-stranded helical organization of these π-amino acids is cooperatively assisted by both CH-π and hydrogen-bond arrays with chirality match. The well-defined spatial arrangement of the π-chromophores could effectively suppress the non-radiative decay pathways and facilitate chiral exciton couplings, leading to superior CPL with a strong figure of merit (glum = 0.14 and QY = 0.76). Our findings might open a new door for developing DNA-inspired chiroptical materials with prominent properties by enantioselective co-assembly initiated double helical π-aggregation.


Immunoblot reactivity of a non-HIV protein with human sera. Transfusion Safety Study Group.
Examination of serum for the presence of antibodies to the human immunodeficiency virus (HIV) by immunoblot analysis requires precise identification of reactivities with various HIV specific proteins. During a recent survey of approximately 2,000 sera, we identified 22 sera from non-HIV-reactive blood donors and 2 from individuals receiving blood products for congenital blood disorders, which consistently and exclusively reacted with a protein of a molecular weight slightly greater than 65,000 daltons (termed AT65). Since the HIV pol p65 protein reacts with specific antibodies at about the same position (i.e., 65,000 daltons), it was essential to determine the viral or nonviral origin of the AT65 reactivity. Our data indicate that the AT65 reaction is due to a protein present on normal or activated lymphocytes, which can co-purify with HIV preparations used for immunoblot analysis. Recognition of HIV-specific p65 and nonspecific AT65 reactions is important to those responsible for interpretation of HIV immunoblots and may aid in the evaluation of some "indeterminant" results.


Prediction of residues in discontinuous B-cell epitopes using protein 3D structures.
Discovery of discontinuous B-cell epitopes is a major challenge in vaccine design. Previous epitope prediction methods have mostly been based on protein sequences and are not very effective. Here, we present DiscoTope, a novel method for discontinuous epitope prediction that uses protein three-dimensional structural data. The method is based on amino acid statistics, spatial information, and surface accessibility in a compiled data set of discontinuous epitopes determined by X-ray crystallography of antibody/antigen protein complexes. DiscoTope is the first method to focus explicitly on discontinuous epitopes. We show that the new structure-based method has a better performance for predicting residues of discontinuous epitopes than methods based solely on sequence information, and that it can successfully predict epitope residues that have been identified by different techniques. DiscoTope detects 15.5% of residues located in discontinuous epitopes with a specificity of 95%. At this level of specificity, the conventional Parker hydrophilicity scale for predicting linear B-cell epitopes identifies only 11.0% of residues located in discontinuous epitopes. Predictions by the DiscoTope method can guide experimental epitope mapping in both rational vaccine design and development of diagnostic tools, and may lead to more efficient epitope identification.


Computed tomographic evaluation of component position on dislocation after total hip arthroplasty.
True proper position after total hip arthroplasty was determined by measuring the cup and stem anteversion using computed tomography. We compared 20 dislocated hips (14 posterior and 6 anterior) with 18 non-dislocated hips. Both the cup anteversion and the stem anteversion showed no differences among the groups. The sum of cup and stem anteversion in posterior dislocated hips was significantly lesser than that in non-dislocated hips and the sum in anterior dislocated hips was significantly greater than that in non-dislocated hips. These results suggested even if the cup alone or the stemalone is at proper position, dislocation might occur.


Durable, safe, multi-gene lentiviral vector expression in feline trabecular meshwork.
Multiple disease-specific considerations have led to interest in the potential of gene therapy to permanently correct elevated intraocular pressure (IOP), the main causal risk factor for primary open angle glaucoma (POAG). Since IOP elevation results from abnormal resistance to aqueous humor outflow from the eye through the trabecular meshwork (TM), a means to genetically modify this specialized outflow organ permanently and safely is a prioritized goal. Here we tested different lentiviral vector designs and doses for long-term transgene expression in a large animal model, and investigated whether exogenously introduced myocilin proteins influenced IOP. The anterior chambers of 18 domestic cats (36 eyes) were injected with dual-gene feline immunodeficiency virus (FIV) vectors. Substantial, well-tolerated green fluorescent protein (GFP) expression was achieved in TM and monitored non-invasively in vivo for 1.2-2.3 years, using both 5' cap-translation and internal ribosome entry site (IRES)-translation. In all 36 eyes, post-mortem examination revealed substantial TM transgene expression (which often greatly exceeded that observable non-invasively during life). However, co-expression with enhanced GFP of myocilin or a juvenile glaucoma-associated mutant myocilin did not elevate IOP. These results demonstrate a safe, long-term single and dual gene expression in TM and establish an experimental system for testing candidate therapeutic transgenes for POAG.


Disposal of radioactive wastes.
Scientists appointed by the International Council of Scientific Unions have concluded that nuclear wastes may be safely disposed of using current technology. Interim storage for 50 to 100 years greatly reduces the problem of thermal loading at the final disposal sites, but more research devoted to such interim storage is needed.


[Usefulness of bevacizumab combination chemotherapy for advanced breast cancer].
Bevacizumab combination chemotherapy prolongs progression-free survival but not overall survival in patients with advanced breast cancer. Here, we report our experience with bevacizumab plus paclitaxel treatment in our department. We believe that this regimen confers some benefit to a patient's quality of life. Nineteen patients with inoperable, metastatic, or recurrent breast cancer were treated with bevacizumab plus paclitaxel. The median age was 55 years; all patients were females. Of the 19 patients, 14, 1, and 4 had luminal A, luminal B, and triple-negative type tumors, respectively. The response rate was 63%: partial response (PR) was obtained in 12 patients, stable disease (SD) in 5 patients, and progressive disease( PD) in 2 patients. Adverse events of Grade 3 or more were high blood pressure( 4 patients), peripheral neuropathy (1 patient), and neutropenia (9 patients). All side effects could be tolerated. There was a high rate of response to bevacizumab plus paclitaxel chemotherapy. We believe that this chemotherapy is useful in patients with more advanced breast cancer in whom a high response rate is required.


Nutritional Composition and Sensory Acceptability of Stinging Nettle (Urtica simensis) Flour-Supplemented Unleavened Maize (Zea mays L.) Flatbread (Kitta).
In Ethiopia, a few studies had been conducted to improve the nutritional values and sensory acceptability of maize-based flatbread. These studies did not address indigenous edible wild green vegetables like stinging nettle (Urtica simensis). Consequently, there was a scientific report gap on the effect of incorporating stinging nettle leaf flour into local staple foods like flatbread. Therefore, this study was intended to investigate the nutritional composition and sensory acceptability of unleavened maize (Zea mays L.) flatbread (Kitta) supplemented with stinging nettle (Urtica simensis) flour. The flatbread was developed from composite flour of germinated maize and nettle leaf in a ratio of 90 : 10, 85 : 15, 80 : 20, and 75 : 25, respectively. Hundred percent (100%) nongerminated maize flour flatbread was used as control. Proximate composition, minerals (Fe, Zn, and Ca), and vitamin C contents were analyzed. The sensory acceptability test was rated by a nine-point hedonic scale. The result revealed that crude protein and fat decreased from 11.02 g to 7.21 g and 1.12 g to 0.48 g, respectively, when the amount of nettle flour supplementation increased from 0% to 25%. On the contrary, total ash, crude fiber, and total carbohydrate slightly increased from 1.84 to 3.81 g, 2.19 to 3.05, and 75.53 to 80.05 g, respectively. The calcium, zinc, and iron content significantly (p < 0.05) increased from 60.51 to 283.74 mg, 5.09 to 9.24 mg, and 1.72 to 3.59 mg when the amount of nettle flour increased from 0% to 25%, respectively. All sensory acceptability tests showed decrement with increasing the amount of nettle flour, but the control group has the highest acceptability.


Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation.
The multidrug transporter permeability (P)-glycoprotein is an adenosine triphosphate (ATP)-binding cassette exporter responsible for clinical resistance to chemotherapy. P-glycoprotein extrudes toxic molecules and drugs from cells through ATP-powered conformational changes. Despite decades of effort, only the structures of the inward-facing conformation of P-glycoprotein are available. Here we present the structure of human P-glycoprotein in the outward-facing conformation, determined by cryo-electron microscopy at 3.4-angstrom resolution. The two nucleotide-binding domains form a closed dimer occluding two ATP molecules. The drug-binding cavity observed in the inward-facing structures is reorientated toward the extracellular space and compressed to preclude substrate binding. This observation indicates that ATP binding, not hydrolysis, promotes substrate release. The structure evokes a model in which the dynamic nature of P-glycoprotein enables translocation of a large variety of substrates.


Depressive symptoms influence use of feedback for motor learning and recovery in chronic stroke.
Sensorimotor impairments and depressive symptoms (PSD) influence arm motor recovery post-stroke. Feedback provision improves upper limb motor learning in patients with chronic stroke but factors including PSD may affect ability to use feedback. We evaluated the influence of PSD on the ability to use auditory feedback for upper limb recovery and motor learning in patients with chronic stroke. Participants (n = 24) practiced 72 pointing movements/session (6 targets, 12 sessions, randomized) with auditory feedback on movement speed and trunk displacement. The presence of PSD (Beck's Depression Inventory; BDI-II) was assessed at pre-intervention (PRE). Arm motor impairment (Fugl-Meyer Assessment, shoulder horizontal adduction, shoulder flexion, elbow extension ranges, trunk displacement) and arm use (Motor Activity Log) were assessed at PRE, immediately after (POST) and retention (3 mos; RET). Participants were divided into two groups based on BDI-II scores: ≥ 14/63 (DEP group; n = 8; score: 20.5 ± 7.5) and ≤ 13/63 (no PSD (ND) group; n = 16; score: 5.0 ± 3.8). Changes in impairment and arm use levels were assessed (mixed-model ANOVAs). All participants improved arm use. DEP had lower Fugl-Meyer scores, used more compensatory trunk displacement and had lower shoulder horizontal adduction range compared to ND. The presence of PSD diminished the ability to use auditory feedback for arm motor recovery and motor learning.


[Effectiveness of tube feeding in neurosurgical patients].
The results of the early use of gastrogavage in 24 neuroresuscitation patients are analysed. The dosage of the feeding and control over its efficacy was exercised by means of appraising energy expenditures and their structure with the use of indirect calorimetry as well as according to the nitrous balance data, biochemical criteria of the alimentary status, and the total lymphocyte count. It is shown that neuroresuscitation patients manifested appreciable changes in energy expenditures and their structure as well. It is fairly embarrassing to meet the energy requirements of such patients with the aid of the routine hospital diet. The early use of gastrogavage with the aid of dry, readily reducible mixtures of the Ensure type, that meet the neuroresuscitation patients' requirements, make intensive care more efficacious.


Association and risk factors of pediatric pulmonary hypertension with obstructive sleep apnea: A national study utilizing the Kids' Inpatient Database (KID).
Assess the prevalence of and risk factors for pediatric pulmonary hypertension (PH) in the 2016 Kids' Inpatient Database (KID), including obstructive sleep apnea (OSA) and obesity. Retrospective cross-sectional cohort study utilizing 6,081,132 weighted pediatric discharges from the 2016 KID. Study variables included age, length of stay, mortality, gender, hospital region, primary payer, race, median household income for patient's ZIP code, OSA, central sleep apnea (CSA), obesity, Down syndrome, sickle cell disease (SCD), thalassemia, congenital heart disease (CHD), hypertension, asthma and chronic lung disease of prematurity (CLDP). PH was the primary outcome of interest. Bivariate and multivariable logistic regression models were utilized with odds ratios and 95 % confidence intervals. The mean age was 3.76 years, the mean hospital length of stay was 3.85 days, 48.9 % were male, 52.6 % had government health insurance, 51.0 % were White, 16.1 % were Black, 21.1 % were Hispanic, 5.0 % were Asian or Pacific Islander, 0.80 % were Native American and 6.1 % identified as "other". The prevalence of PH was 0.21 % (12,777 patients). There were 37,631 patients with OSA and the prevalence of PH among this cohort was 3.3 %, over 10x greater than the overall prevalence of PH in the 2016 KID (0.21 %). Risk factors associated with PH included CLDP, CHD, Down syndrome, asthma, OSA, CSA, hypertension, SCD, obesity, race/ethnicity, government insurance, age, male gender (p < 0.0001), and hospital region (p = 0.0002). Several risk factors were independently associated with PH, such as OSA, CSA, obesity, asthma, and insurance status. Prospective multi-institutional studies are needed to assess the relationships between these risk factors, severity metrics, and causative links in the development of PH; in addition to identifying children with OSA who are most likely to benefit from cardiopulmonary screening prior to adenotonsillectomy. Level III.


Spatio-temporal expression of candidate genes for nectar spur development in Tropaeolum (Tropaeolaceae: Brassicales).
Tropaeolaceae (Brassicales) comprise ca. 100 species native to South and Central America. Tropaeolaceae flowers have a nectar spur, formed by a late expansion and evagination of the fused proximal region of the perianth (i.e. the floral tube). This spur is formed in the domain of the tube oriented towards the inflorescence axis, which corresponds to the adaxial floral region. However, little is known about the molecular mechanisms responsible for the evolution of spurs in Tropaeolaceae. In this study, we examined the spatio-temporal expression of genes putatively responsible for differential patterns of cell division between the adaxial and abaxial floral regions in Tropaeolaceae. These genes include previously identified TCP and KNOX transcription factors, and the cell division marker HISTONE H4 (HIS4). We found a TCP4 homolog concomitantly expressed with spur initiation and elaboration. Tropaeolaceae possess two TCP4-like (TCP4L) copies, as a result of a Tropaeolaceae-specific duplication. The two copies (TCP4L1 and TCP4L2) in Tropaeolum longifolium show overlapping expression in the epidermis of reproductive apices (inflorescence meristems) and young floral buds, but only TlTCP4L2 shows differential expression in the floral tube at early stages of spur formation, restricted to the adaxial region. This adaxial expression of TlTCP4L2 overlaps with the expression of TlHIS4. Later in development, only TlTCP4L2 is expressed in the nectariferous tissue of the spur. Based on these results, we hypothesize that Tropaeolaceae TCP4L genes had a plesiomorphic role in epidermal development and that, after gene duplication, TCP4L2 acquired a new function in spur initiation and elaboration. To better understand spur evolution in Tropaeolaceae, it is critical to expand developmental genetic studies to their sister group, the Akaniaceae, which possess simultaneously an independent duplication of TCP4L genes, and a spurless floral tube.


The Anti-Inflammatory Mediator 17(R)-Resolvin D1 Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis.
Increased inflammation contributes to pressure overload-induced myocardial remodeling. 17(R)-Resolvin D1 (17(R)-RvD1), a potent lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties. However, the association between 17(R)-RvD1 and pressure overload-induced cardiac hypertrophy remains unclear. Transverse aortic constriction (TAC) surgery was performed to establish a cardiac hypertrophy model. C57BL/6J mice were randomly assigned to the Sham, TAC and TAC+17(R)-RvD1 groups. 17(R)-RvD1 was injected (2 μg/kg, i.p.) before TAC surgery and once every other day after surgery for 4 weeks. The same volume of saline was injected into the mice in both Sham group and TAC group. Then, cardiac function was evaluated and heart tissues were collected for biological analysis. 17(R)-RvD1 treatment attenuated TAC-induced increase in left ventricular diameter and decrease in left ventricular contractility, mitigated increased cardiomyocyte cross-sectional area, and downregulated the expression of hypertrophic genes. Besides, 17(R)-RvD1 attenuated myocardial fibrosis, as indicated by the decreased LV collagen volume and expression of fibrotic genes. In addition, 17(R)-RvD1 ameliorated the inflammatory response in cardiac tissue, as illustrated by the decreased infiltration of CD68+ macrophages and reduced production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. 17(R)-RvD1 treatment significantly suppressed the activation of NLRP3 inflammasome after TAC surgery, which might be responsible for the attenuation of inflammation in cardiac tissue. 17(R)-RvD1 attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and the possible mechanism may be associated with the inhibition of NLRP3 inflammasome. 17(R)-RvD1 may serve as a potential drug for the treatment of cardiac hypertrophy.


Object-based attention modulates the discrimination of level increments in stop-consonant noise bursts.
This study tested the hypothesis that object-based attention modulates the discrimination of level increments in stop-consonant noise bursts. With consonant-vowel-consonant (CvC) words consisting of an ≈80-dB vowel (v), a pre-vocalic (Cv) and a post-vocalic (vC) stop-consonant noise burst (≈60-dB SPL), we measured discrimination thresholds (LDTs) for level increments (ΔL) in the noise bursts presented either in CvC context or in isolation. In the 2-interval 2-alternative forced-choice task, each observation interval presented a CvC word (e.g., /pæk/ /pæk/), and normal-hearing participants had to discern ΔL in the Cv or vC burst. Based on the linguistic word labels, the auditory events of each trial were perceived as two auditory objects (Cv-v-vC and Cv-v-vC) that group together the bursts and vowels, hindering selective attention to ΔL. To discern ΔL in Cv or vC, the events must be reorganized into three auditory objects: the to-be-attended pre-vocalic (Cv-Cv) or post-vocalic burst pair (vC-vC), and the to-be-ignored vowel pair (v-v). Our results suggest that instead of being automatic this reorganization requires training, in spite of using familiar CvC words. Relative to bursts in isolation, bursts in context always produced inferior ΔL discrimination accuracy (a context effect), which depended strongly on the acoustic separation between the bursts and the vowel, being much keener for the object apart from (post-vocalic) than for the object adjoining (pre-vocalic) the vowel (a temporal-position effect). Variability in CvC dimensions that did not alter the noise-burst perceptual grouping had minor effects on discrimination accuracy. In addition to being robust and persistent, these effects are relatively general, evincing in forced-choice tasks with one or two observation intervals, with or without variability in the temporal position of ΔL, and with either fixed or roving CvC standards. The results lend support to the hypothesis.


Deep learning combined with IAST to screen thermodynamically feasible MOFs for adsorption-based separation of multiple binary mixtures.
The structures of metal-organic frameworks (MOFs) can be tuned to reproducibly create adsorption properties that enable the use of these materials in fixed-adsorption beds for non-thermal separations. However, with millions of possible MOF structures, the challenge is to find the MOF with the best adsorption properties to separate a given mixture. Thus, computational, rather than experimental, screening is necessary to identify promising MOF structures that merit further examination, a process traditionally done using molecular simulation. However, even molecular simulation can become intractable when screening an expansive MOF database for their separation properties at more than a few composition, temperature, and pressure combinations. Here, we illustrate progress toward an alternative computational framework that can efficiently identify the highest-performing MOFs for separating various gas mixtures at a variety of conditions and at a fraction of the computational cost of molecular simulation. This framework uses a "multipurpose" multilayer perceptron (MLP) model that can predict single component adsorption of various small adsorbates, which, upon coupling with ideal adsorbed solution theory (IAST), can predict binary adsorption for mixtures such as Xe/Kr, CH4/CH6, N2/CH4, and Ar/Kr at multiple compositions and pressures. For this MLP+IAST framework to work with sufficient accuracy, we found it critical for the MLP to make accurate predictions at low pressures (0.01-0.1 bar). After training a model with this capability, we found that MOFs in the 95th and 90th percentiles of separation performance determined from MLP+IAST calculations were 65% and 87%, respectively, the same as MOFs in the simulation-predicted 95th percentile across several mixtures at diverse conditions (on average). After validating our MLP+IAST framework, we used a clustering algorithm to identify "privileged" MOFs that are high performing for multiple separations at multiple conditions. As an example, we focused on MOFs that were high performing for the industrially relevant separations 80/20 Xe/Kr at 1 bar and 80/20 N2/CH4 at 5 bars. Finally, we used the MOF free energies (calculated on our entire database) to identify privileged MOFs that were also likely synthetically accessible, at least from a thermodynamic perspective.


Calcium Regulates the Nuclear Localization of Protein Arginine Deiminase 2.
Protein arginine deiminases (PADs) are calcium-dependent enzymes that mediate the post-translational conversion of arginine into citrulline. Dysregulated PAD activity is associated with numerous autoimmune disorders and cancers. In breast cancer, PAD2 citrullinates histone H3R26 and activates the transcription of estrogen receptor target genes. However, PAD2 lacks a canonical nuclear localization sequence, and it is unclear how this enzyme is transported into the nucleus. Here, we show for the first time that PAD2 translocates into the nucleus in response to calcium signaling. Using BioID2, a proximity-dependent biotinylation method for identifying interacting proteins, we found that PAD2 preferentially associates with ANXA5 in the cytoplasm. Binding of calcium to PAD2 weakens this cytoplasmic interaction, which generates a pool of calcium-bound PAD2 that can interact with Ran. We hypothesize that this latter interaction promotes the translocation of PAD2 into the nucleus. These findings highlight a critical role for ANXA5 in regulating PAD2 and identify an unusual mechanism whereby proteins translocate between the cytosol and nucleus.


SNP Polymorphism in Genomes of CC320 Isolates of Streptococcuspneumoniae Resistant to Beta-Lactams.
Bioinformatic analysis of the data on the genome sequencing of the isolates of the Streptococcuspneumoniae clonal complex SS320 from the Russian Federation, as well as the data on SS320 isolates from public sources in the penicillin resistant isolates resulted in detection of 139 missense mutations in 45 genes. In addition to the mutations in the genes of the main penicillin-binding proteins (PSB - PBP1A, PBP2B and PBP2X) there was detected high frequency of mutations in the genes of the (division and cell wall) dcw-cluster, as well as in RegR protein belonging to the transcription regulators of the LacI/GaIR family. Development of resistance to beta-lactams in S.pneumoniae is defined not only by modification of the PSB, but also by adaptive changes in the metabolic pathways involved in the bacterial cell growth and division.


Evaluation of parameters influencing the molecular delivery by biodegradable microsphere-mediated perforation using femtosecond laser.
The parameters critically influencing the delivery rate on the biodegradable microsphere-mediated femtosecond (fs) laser perforation are investigated in detail with the aim of developing efficient molecular delivery. Cell membrane was perforated by the irradiation of weakly focused fs laser pulses to the spherical polylactic acid microspheres conjugated to the cell membrane. The delivery of fluorescein isothiocyanate-dextran and fluorescent silica particles to A431 cells is investigated in detail. The increase in the number of irradiated laser pulses had resulted in the increase of delivery rate. The delivery rate depends on the size and functionalization of fluorescent silica particles in which silica particles of 100 nm in diameter were able to be delivered into 20% of the irradiated cells, suggesting that the pore sizes are large enough for the delivery of therapeutic agents into cells. These findings contribute to the development of an efficient and safe phototherapy and drug delivery.


Knowledge, attitudes and beliefs about contraceptive and sexual consent negotiation among college women.
College women have the highest rates of sexual violence, sexually transmitted infections, and unintended pregnancy compared with women in all other age groups. Although much is known about sexual risk behaviors among college women, less is known about how women negotiate consent for contraceptive use during sexual encounters. Therefore, the purpose of this qualitative descriptive study was to explore college women's knowledge, attitudes, and beliefs about contraceptive and sexual consent during dating relationships. Twenty-six women participated in five focus groups on two college campuses in the northeastern United States. Content analysis was used to analyze the data. The three main categories that emerged from the analysis included the influence of alcohol on sexual behaviors, lack of negotiation for sexual consent and contraceptive use, and fear of pregnancy. The results of this study highlight the complex social interactions and norms that college women encounter when making decisions regarding sexual activity and contraceptive use. The results of this study can inform the role of college health providers and forensic nurses to promote sexual health and safety when they interact with college women.


Application of echocardiography on transgenic mice with cardiomyopathies.
Cardiomyopathies are common cardiac disorders that primarily affect cardiac muscle resulting in cardiac dysfunction and heart failure. Transgenic mouse disease models have been developed to investigate the cellular mechanisms underlying heart failure and sudden cardiac death observed in cardiomyopathy cases and to explore the therapeutic outcomes in experimental animals in vivo. Echocardiography is an essential diagnostic tool for accurate and noninvasive assessment of cardiac structure and function in experimental animals. Our laboratory has been among the first to apply high-frequency research echocardiography on transgenic mice with cardiomyopathies. In this work, we have summarized our and other studies on assessment of systolic and diastolic dysfunction using conventional echocardiography, pulsed Doppler, and tissue Doppler imaging in transgenic mice with various cardiomyopathies. Estimation of embryonic mouse hearts has been performed as well using this high-resolution echocardiography. Some technical considerations in mouse echocardiography have also been discussed.


Regulation of cellular interactions with laminin by integrin cytoplasmic domains: the A and B structural variants of the alpha 6 beta 1 integrin differentially modulate the adhesive strength, morphology, and migration of macrophages.
Several integrin alpha subunits have structural variants that are identical in their extracellular and transmembrane domains but that differ in their cytoplasmic domains. The functional significance of these variants, however, is unknown. In the present study, we examined the possibility that the A and B variants of the alpha 6 beta 1 integrin laminin receptor differ in function. For this purpose, we expressed the alpha 6A and alpha 6B cDNAs, as well as a truncated alpha 6 cDNA (alpha 6-delta CYT) in which the cytoplasmic domain sequence was deleted after the GFFKR pentapeptide, in P388D1 cells, an alpha 6 deficient macrophage cell line. Populations of stable alpha 6A, alpha 6B, and alpha 6-delta CYT transfectants that expressed equivalent levels of cell surface alpha 6 were obtained by fluorescence-activated cell sorter and shown to form heterodimers with endogenous beta 1 subunits. Upon attachment to laminin, the alpha 6A transfectants extended numerous pseudopodia. In contrast, the alpha 6B transfectants remained rounded and extended few processes. The transfectants were also examined for their ability to migrate toward a laminin substratum using Transwell chambers. The alpha 6A transfectants were three- to fourfold more migratory than the alpha 6B transfectants. The alpha 6-delta CYT transfectants did not attach to laminin in normal culture medium, but they did attach in the presence of Mn2+. The alpha 6-delta CYT transfectants migrated to a lesser extent than either the alpha 6A or alpha 6B transfectants in the presence of Mn2+. The alpha 6 transfectants differed significantly in the concentration of substratum bound laminin required for half-maximal adhesion in the presence of Mn2+:alpha 6A (2.1 micrograms/ml), alpha 6B (6.3 micrograms/ml), and alpha 6-delta CYT (8.8 micrograms/ml). Divalent cation titration studies revealed that these transfectants also differed significantly in both the [Ca2+] and [Mn2+] required to obtain half-maximal adhesion to laminin. These data demonstrate that the A and B variants of the alpha 6 cytoplasmic domain can differentially modulate the function of the alpha 6 beta 1 extracellular domain.


Gunshot wounds to the ureter.
Since our last review 17 more patients have been treated for ureteral gunshot injuries. In six cases the upper ureter, in two the middle, and in nine cases the lower ureter was involved. Associated visceral injuries were numerous with the small intestine the most commonly injured. In over 50% of the injuries to the lower ureter, the iliac vein was injured. In three patients the ureter was the only major structure involved. There was no hospital mortality. Optimal surgical repair done by generous resection, primary end-to-end anastomosis and stenting and drainage via a proximal ureteral T-tube gave excellent results and no longterm complications in a population subject to careful short and longterm followup. While an uncommon injury, the principles of effective repair are clear and must be applied in the face of serious associated disorders to continue these satisfactory results.


Flow cytometric measurement of platelet-leukocyte aggregates: a possible target to monitor platelet function?
Increased platelet-leukocyte-aggregate (PLA) formation has been reported in acute coronary syndromes (ACS) and during cardiopulmonary bypass, and PLA formation has been acknowledged as a possible target for antiplatelet therapy in ACS and coronary interventions. It has also been suggested as a monitoring tool for risk stratification parameters. In a controlled study design as well as under clinical conditions we investigated the effect of antiplatelet agents by flow cytometric measurement of PLA formation. We were able to demonstrate considerable reduction in PLA formation under experimental and clinical clopidogrel therapy alone or in combination with aspirin. In healthy volunteers the percentage of monocyte-PLAs decreased significantly to 55 to 75% of the baseline under clopidogrel, depending on the type and concentration of the activating agent. In patients with severe peripheral artery disease, formation of monocyte-PLAs at baseline and after stimulation with thrombin receptor activating peptide (TRAP) or adenosine diphosphate (ADP) was significantly lower under combined therapy when compared with patients under aspirin alone or without antiplatelet treatment. Flow cytometric measurement of PLA formation appears to be well suited for dose response of antiplatelet agents in healthy volunteers and a valuable tool in establishing the clinical significance of circulating PLAs. It may also be a qualified method to monitor platelet function in long-term treatment with antiplatelet agents that interfere with the degranulation process. It is not suited for acute situations.


Current and future therapy for chronic hepatitis C virus liver disease.
Therapy with recombinant human interferon alpha remains pivotal to the treatment for chronic hepatitis C virus liver disease. Semi-synthetic protein-polymer conjugates of interferon with polyethylene glycol have also been recently developed. These conjugates protect the protein from degradation; reduce the immunogenicity; and prolong exposure to drug by a sustained absorption, restricted volume of distribution and sustained high serum concentration. Therapy with pegylated interferons is associated with significantly greater sustained virological response rates (SVR) compared to the non-pegylated formulation. Ribavirin is a guanosine analog with minimal antiviral activity against HCV. It demonstrates significant clinical synergism when administered in combination with interferon. Amantadine blocks entry of influenza A virus into cells. Used in combination with ribavirin and interferon as triple therapy, it may have some benefit compared to dual or monotherapy. Current treatment with pegylated interferons combined with weight-based ribavirin, provides the highest sustained virological response rates. In the absence of suitable animal models, HCV dynamic studies in man have been helpful in defining the mechanisms of action of interferon in chronic HCV liver disease. Novel therapeutic agents are being developed as the replication cycle of HCV is being understood. However, their safety and efficacy remain to be established and availability for clinical use is unlikely within the next 3 to 5 years. This review describes current antiviral therapy in chronic HCV liver disease, addresses the potential role of viral dynamics in elucidating the mechanisms of action of the drugs and discusses future potential therapeutics agents.


Case of Lumbar Schwannoma Presenting with Isolated Signs and Symptoms of Intracranial Hypertension.
Hydrocephalus and intracranial hypertension are rare signs of spinal tumors when presenting in isolation, particularly with benign tumors. Herein reported is a case of a 53-year-old woman who presented with headache, blurry vision, communicating hydrocephalus, and intracranial hypertension. No primary intracranial pathology was identified, and there were no clinical signs or symptoms of intraspinal pathology. Lumbar puncture revealed elevated opening pressure, cerebrospinal fluid protein, and suspected tumor cells in the cerebrospinal fluid, thus prompting spinal imaging. A primary lumbar schwannoma was subsequently determined to underlie her symptoms, which resolved with tumor resection. Clinical suspicion of spinal pathology should be maintained in patients with unexplained intracranial hypertension, even in the absence of localizing signs of spinal pathology.


Childhood predictors of cardiovascular disease in adulthood. A systematic review and meta-analysis.
Childhood obesity predicts the risk of adult adiposity, which is associated with the earlier onset of cardiovascular disease [adult atherosclerotic cardiovascular disease, ACVD: hypertension, increased carotid intima media thickness (CIMT) stroke, ischemic heart disease (IHD)] and dysglycaemia. Because it is not known whether childhood obesity contributes to these diseases, we conducted a systematic review of studies that examine the ability of measures of obesity in childhood to predict dysglycaemia and ACVD. Data sources were Web of Science, MEDLINE, PubMed, CINAHL, Cochrane, SCOPUS, ProQuest and reference lists. Studies measuring body mass index (BMI), skin fold thickness and waist circumference were selected; of 1,954 studies, 18 met study criteria. Childhood BMI predicted CIMT: odds ratio (OR), 3.39 (95% confidence interval (CI), 2.02 to 5.67, P < 0.001) and risk of impaired glucose tolerance in adulthood, but its ability to predict ACVD events (stroke, IHD; OR, 1.04; 95% CI, 1.02 to 1.07; P < 0.001) and hypertension (OR, 1.17, 95% CI 1.06 to 1.27, P = 0.003) was weak-moderate. Body mass index was not predictive of systolic BP (r -0.57, P = 0.08) and weakly predicted diastolic BP (r 0.21, P = 0.002). Skin fold thickness in childhood weakly predicted CIMT in female adults only (rs 0.09, P < 0.05). Childhood BMI predicts the risk of dysglycaemia and abnormal CIMT in adulthood, but its ability to predict hypertension and ACVD events was weak and moderate, respectively. Skin fold thickness was a weak predictor of CIMT in female adults.


Comparing dosing of basal insulin analogues detemir and glargine: is it really unit-per-unit and dose-per-dose?
To review the available evidence regarding dosing conversion between glargine and detemir in an effort to assist clinicians in performing dosing conversion. A MEDLINE literature search was performed using the search terms glargine and detemir for articles published through August 2013. All English-language clinical trials were reviewed for inclusion of dosing and/or pharmacokinetic data. A total of 7 large (n ≥ 258) randomized controlled trials (RCTs) comparing glargine and detemir in patients with type 1 and 2 diabetes had dosing equivalency data available. In these 7 RCTs, on average, a 38% higher detemir dose was required (range = 8.0%-77.2%) to achieve glucose control comparable to that achieved with glargine. A 24-hour isoglycemic clamp study conducted in 11 patients with type 1 diabetes demonstrated that the duration of action of detemir is dose dependent, with increasing doses of detemir resulting in increased duration of action of detemir. Pharmacokinetic studies conducted in patients with type 2 diabetes are conflicting, although the majority of evidence suggests that glargine provides a longer duration of glycemic control as compared with detemir. When performing conversion between glargine and detemir, prescribers should be aware that higher doses of detemir as compared with glargine may be necessary to achieve the same glycemic control. Additionally, twice-daily injections of detemir should be considered in clinical situations in which glucose control appears to decline after 12 hours, especially with doses ≤0.4 units/kg/d in patients with type 1 diabetes.


The CUE Domain of Cue1 Aligns Growing Ubiquitin Chains with Ubc7 for Rapid Elongation.
Ubiquitin conjugation is an essential process modulating protein function in eukaryotic cells. Surprisingly, little is known about how the progressive assembly of ubiquitin chains is managed by the responsible enzymes. Only recently has ubiquitin binding activity emerged as an important factor in chain formation. The Ubc7 activator Cue1 carries a ubiquitin binding CUE domain that substantially stimulates K48-linked polyubiquitination mediated by Ubc7. Our results from NMR-based analysis and in vitro ubiquitination reactions point out that two parameters accelerate ubiquitin chain assembly: the increasing number of CUE binding sites and the position of CUE binding within a growing chain. In particular, interactions with a ubiquitin moiety adjacent to the acceptor ubiquitin facilitate chain elongation. These data indicate a mechanism for ubiquitin binding in which Cue1 positions Ubc7 and the distal acceptor ubiquitin for rapid polyubiquitination. Disrupting this mechanism results in dysfunction of the ERAD pathway by a delayed turnover of substrates.


Evidence of genetic overlap of schizophrenia and bipolar disorder: linkage disequilibrium analysis of chromosome 18 in the Costa Rican population.
The long-standing concept that schizophrenia (SC) and bipolar disorder (BP) represent two distinct illnesses has been recently challenged by findings of overlap of genetic susceptibility loci for these two diseases. We report here the results of a linkage disequilibrium (LD) analysis of chromosome 18 utilizing subjects with SC from the Central Valley of Costa Rica. Evidence of association (P < 0.05) was obtained in three chromosomal regions: 18p11.31 (D18S63), 18q12.3 (D18S474), and 18q22.3-qter (D18S1161, D18S70), all of which overlap or are in close proximity with loci previously shown to be in LD with BP, type I in this population. Since both the SC and bipolar samples contained cases with a history of mania and almost all cases of SC and BP had a history of psychosis, we performed an alternative phenotyping strategy to determine whether presence or absence of mania, in the context of psychosis, would yield distinct linkage patterns along chromosome 18. To address this issue, a cohort of psychotic patients (including a range of DSMIV diagnoses) was divided into two groups based on the presence or absence of mania. Regions that showed association with SC showed segregation of association when the sample was stratified by history of mania. Our results are compared with previous genetic studies of susceptibility to SC or BP, in Costa Rica as well as in other populations. This study illustrates the importance of detailed phenotype analysis in the search for susceptibility genes influencing complex psychiatric disorders in isolated populations and suggests that subdivision of psychoses by presence or absence of past mania syndromes may be useful to define genetic subtypes of chronic psychotic illness.


Qualitative Review on Domains of Quality of Life Important for Patients, Social Care Users, and Informal Carers to Inform the Development of the EQ-HWB.
To identify the themes to inform the content of a new generic measure, the EQ-HWB (EQ Health and Wellbeing), that can be used in economic evaluation across health, social care, and public health, based on the views of users and beneficiaries of these services including informal carers. A qualitative review was undertaken. Systematic and citation searches were undertaken focusing on qualitative evidence of the impact on quality of life from reviews for selected health conditions, informal carers, social care users, and primary qualitative work used in the development of selected measures. A subset of studies was included in the review. Framework analysis and synthesis were undertaken based on a conceptual model. A total of 42 reviews and 24 primary studies were selected for inclusion in the review. Extraction and synthesis resulted in 7 high-level themes (with subthemes): (1) feelings and emotions (sadness, anxiety, hope, frustration, safety, guilt/shame); (2) cognition (concentration, memory, confusion, thinking clearly); (3) self-identity (dignity/respect, self-esteem); (4) "coping, autonomy, and control" relationships; (5) social connections (loneliness, social engagement, stigma, support, friendship, belonging, burden); (6) physical sensations (pain, discomfort, sleep, fatigue); and (7) activity (self-care, meaningful activities, mobility, communication, hearing, vision). Apart from physical sensations, most of the other themes and subthemes were relevant across both health and social care, including for informal carers. The findings from this broad review identified themes that go beyond health and that are relevant to patients, informal carers, and social care users. The themes and subthemes informed the domains for the EQ-HWB.


Triggering of TLR-3, -4, NOD2, and DC-SIGN reduces viral replication and increases T-cell activation capacity of HIV-infected human dendritic cells.
A variety of signals influence the capacity of dendritic cells (DCs) to mount potent antiviral cytotoxic T-cell (CTL) responses. In particular, innate immune sensing by pathogen recognition receptors, such as TLR and C-type lectines, influences DC biology and affects their susceptibility to HIV infection. Yet, whether the combined effects of PPRs triggering and HIV infection influence HIV-specific (HS) CTL responses remain enigmatic. Here, we dissect the impact of innate immune sensing by pathogen recognition receptors on DC maturation, HIV infection, and on the quality of HS CTL activation. Remarkably, ligand-driven triggering of TLR-3, -4, NOD2, and DC-SIGN, despite reducing viral replication, markedly increased the capacity of infected DCs to stimulate HS CTLs. This was exemplified by the diversity and the quantity of cytokines produced by HS CTLs primed by these DCs. Infecting DCs with viruses harboring members of the APOBEC family of antiviral factors enhanced the antigen-presenting skills of infected DCs. Our results highlight the tight interplay between innate and adaptive immunity and may help develop innovative immunotherapies against viral infections.


Phosphoproteome profiling reveals critical role of JAK-STAT signaling in maintaining chemoresistance in breast cancer.
Breast cancer is responsible for 25% of cancer cases and 15% of cancer death among women. Treatment is usually prolonged and hampered by the development of chemoresistance. The molecular mechanisms maintaining the chemoresistant phenotype remains, however, largely obscure. As kinase signaling in general is highly drugable, identification of kinases essential for maintaining chemoresistance could prove therapeutically useful. Hence we compared cellular kinase activity in chemotherapy resistant MCF7Res cells to chemotherapy-sensitive MCF cells using a peptide array approach that provides an atlas of cellular kinase activities and consequently, predominant pathways can be identified. We observed that peptides phosphorylated by elements of JAK-STAT signaling pathway and PKC signaling pathways are subject to extensive kinase activity in MCF7Res cells as compared to chemotherapy-sensitive MCF cells; and Western blotting confirmed relatively strong activation of these signaling pathways in chemoresistant cells. Importantly, treatment of cells with Tofacitinib, a FDA-approved JAK inhibitor, converted chemoresistant cells to chemosensitive cells, inducing apoptosis when used in conjunction with doxorubicin. Thus our results reveal that chemoresistance in breast cancer is associated with activation of JAK/STAT signaling and suggest that JAK2 may be useful for combating chemoresistance in breast cancer.


[Computer-assisted analysis of sperm morphology in veterinary medicine].
The evaluation of spermatozoal morphology is an essential step to determine the fertility potential in male individuals. The method of computer-assisted morphometry provides an efficient tool to evaluate objectively morphological anomalies of the sperm head. This review describes the development and current status of morphometry systems and addresses the various problems associated with this method in veterinary medicine. Although there are some unanswered questions, a number of interesting results have been obtained. In all species investigated an individual influence on sperm head dimensions could be demonstrated. In the bull the extent of variability rather than absolute morphometric data is related to individual fertility. The method of computer-assisted morphometry will also help to develop well defined criteria for subjective evaluation of sperm morphology. Further research has to be directed towards the evaluation of the sperm mid-piece. The ultimate goal is the automatic determination of spermatozoal morphology.


[Comprehensive clinical study on pathogenesis of early spontaneous abortion].
Clinical studies on the natural history of early spontaneous abortion included ultrasonic examination of the conceptus, determination of serum human chorionic gonadotropin beta (H), evaluation of trophoblast viability (V), chromosomal analysis of chorionic tissue and assessment of the mixed lymphocyte reaction-blocking effect (BE) of serum in 22 cases with missed abortion and 4 with incomplete abortion. TV was evaluated by simultaneous staining with fluorescein diacetate-propidium iodide (FDA-PI). The data obtained were as follows: 1) Chromosomal abnormalities were observed in 13 of 21 patients analyzed. 2) V was 78.6 +/- 5.6 (n = 7) in induced abortion, 42.3 +/- 16.2 (n = 22) in missed abortion and 8.8 +/- 4.8 (n = 4) in incomplete abortion. 3) There was a significant linear correlation between the maximum diameter of the gestational sac (D) and the weight of the chorionic tissue (W) (W = 1.30 + 0.08D, r = 0.44, p less than 0.05), and between the titer of H and the weight of the viable chorionic tissue (Wv = W x V) (Wv = 0.66 + 0.01H, r = 0.77, p less than 0.01). Consequently, the following formula was devised: V = (H + 66)/(0.08D + 1.30). 4) Results obtained from the formula indicated that V stays at an elevated level for some time and then falls gradually or rapidly after fetal death in spontaneous abortion. 5) Spontaneous expulsion of the conceptus occurred when V declined to about 10% in 4 cases. 6) There was a significant linear correlation between BE and V (V = 34.58 + 0.31BE, r = 0.45, p less than 0.05). It was thus concluded that the intrauterine retention period of the conceptus after fetal death is dependent on V, which can be estimated by D, H and BE in spontaneous abortion.


Role of the Death Receptor and Endoplasmic Reticulum Stress Signaling Pathways in Polyphyllin I-Regulated Apoptosis of Human Hepatocellular Carcinoma HepG2 Cells.
Polyphyllin has been reported to exhibit anticancer effects against various types of cancer via the proapoptotic signaling pathway. The aim of the present study was to investigate the role of the endoplasmic reticulum stress and death receptor signaling pathways in PPI-induced apoptosis of human hepatocellular carcinoma HepG2 cells. Analysis demonstrated that PPI could significantly inhibit the proliferation and induce apoptosis of HepG2 cells in a dose- and time-dependent manner. Investigation into the molecular mechanism of PPI indicated that PPI notably mediated ER stress activation via IRE-1 overexpression and activation of the caspase-12 to protect HepG2 cells against apoptosis. In addition, PPI markedly induced the expression of death receptors signaling pathways-associated factors, including tumor necrosis factor (TNF) receptor 1/TNF-α and FAS/FASL. Additionally, suppression of the death receptor signaling pathways with a caspase-8 inhibitor, Z-IETD-FMK, revealed an increase in the death rate and apoptotic rate of HepG2 cells. Collectively, the findings of the present study suggested that the ER stress and death receptor signaling pathways were associated with PPI-induced HepG2 cell apoptosis; however, endoplasmic reticulum stress may serve a protective role in this process. The combination of PPI and Z-IETD-FMK may activate necroptosis, which enhances apoptosis. Therefore, the results of the present study may improve understanding regarding the roles of signaling pathways in PPI regulated apoptosis and contribute to the development of novel therapies for the treatment of HCC.


Physiologic Specialization of Puccinia triticina on Wheat in the United States in 2016.
Leaves of wheat infected with the leaf rust fungus Puccinia triticina were obtained from farm fields and breeding plots at experimental stations in the Great Plains, Ohio River Valley, and southeastern states in 2016 in order to identify virulence phenotypes prevalent in the United States in different wheat-growing regions. In total, 496 single uredinial isolates derived from the leaf rust collections were tested for virulence to 20 lines of Thatcher wheat that differ for single leaf rust resistance genes. In total, 71 virulence phenotypes were described in the United States in 2016. The three most common virulence phenotypes across the United States were MBTNB, MBDSD, and TNBJJ. Phenotype MBTNB is virulent to Lr11, and was most common in the soft red winter wheat region of the southeastern states and Ohio Valley. Phenotype MBDSD is virulent to Lr17 and Lr39, and was most common in the hard red winter wheat area of the southern Great Plains. Phenotype TNBJJ is virulent to Lr24 and Lr39, which are present in the hard red winter wheat cultivars. The P. triticina population in the United States was characterized by two major regional groups of virulence phenotypes in the Great Plains region where hard red winter and spring wheat cultivars are grown, and in the southeastern states and Ohio Valley region where soft red winter wheat cultivars are grown. Isolates from New York State differed the most for virulence compared with the other two major regions.


Peripheral Muscle Strength Indicates Respiratory Function Testing in Renal Recipients.
Muscle wasting occurs in renal recipients due to decreased physical performance, and decreased respiratory muscle strength may occur due to changes in structure and function. Data are scarce regarding the roles of sarcopenia and nutritional status on respiratory muscle function in these patients. Here, we evaluated interactions among peripheral muscle strength, sarcopenia, nutritional parameters, and respiratory muscle function in renal transplant recipients. Ninety-nine patients were prospectively enrolled between September and April 2016 at Baskent University. Forced vital capacity values (via pulmonary function tests), respiratory muscle strength (via maximal static inspiratory and expiratory pressures), and peripheral muscle strength (via hand grip strength test) were recorded. Nutritional parameters, fat weight, arm circumference, waist circumference, and C-reactive protein levels were also recorded. Of 99 patients, 68 were renal transplant recipients (43 men, mean age: 39.09 ± 10.70 y) and 31 were healthy participants (14 men, mean age: 34.94 ± 10.95 y). Forced vital capacity (P < .001, r = 0.65), maximal inspiratory (P = .002, r = 0.39) and expiratory (P < .001, r = 0.4) pressure, and hand grip strength showed significant relations in transplant recipients. Positive correlations were found between serum albumin levels and both hand grip strength (P = .16, r = 0.347) and forced vital capacity (P = .03, r = 0.436). Forced vital capacity was statistically different between renal recipients and healthy participants (P = .013), whereas maximal inspiratory and expiratory pressures were not (P > .05). No statistically significant relation was observed between biochemical parameters and maximal inspiratory and expiratory pressures (P ? .05). Respiratory function and peripheral muscle strength were significantly related in renal transplant recipients, with significantly lower peripheral muscle strength suggesting the presence of inadequate respiratory function. Peripheral and respiratory muscle training and nutritional replacement strategies could help to improve postoperative respiratory function.


Establishment of age- and -gender specific reference intervals for amino acids and acylcarnitines by tandem mass spectrometry in Turkish paediatric population.
We determined age- and gender-specific reference intervals (RIs) for acylcarnitines and amino acids by tandem mass spectrometry (MS/MS) in the Turkish paediatric population by using laboratory information system (LIS) data. A total of 9156 MS/MS results of children between 0-18 years of age, were downloaded from the LIS. Premature infants and newborns followed in the intensive care unit were excluded and only the first result of each patient attending outpatient clinics was included. Children with a known or suspected diagnosis of metabolic disease, malignancy, epilepsy, mental retardation, or genetic disorder were excluded. Laboratory results were evaluated and children with any pathological laboratory finding were excluded, resulting in a final sample size of 3357 (2029 boys and 1328 girls). Blood was collected by capillary puncture and spotted on Whatman 903 filter paper cards and analysed by MS/MS (Shimadzu LCMS-8050, Shimadzu Corporation, Kyoto, Japan). Data were evaluated for age and gender differences and age partitioning was performed according to the literature and visual evaluation of the data. Age subgroups were: ≤ 1 month, 2 months-1 year, 2-5 years, 6-10 years, and 11-18 years. There were significant age-related differences for the majority of amino acids and acylcarnitines thus age dependent RIs were established. Gender-specific RIs were established for tyrosine, leucine-isoleucine, isovalerylcarnitine (C5) and hexadecanoylcarnitine (C16). Establishing age-related RIs can enhance the quality of medical care by facilitating early diagnosis and therapy, especially in certain metabolic disorders presenting with mild biochemical abnormalities and subtle clinical manifestations.


TRIB1 downregulates hepatic lipogenesis and glycogenesis via multiple molecular interactions.
Mammalian tribbles homolog 1 (TRIB1) regulates hepatic lipogenesis and is genetically associated with plasma triglyceride (TG) levels and cholesterol, but the molecular mechanisms remain obscure. We explored these mechanisms in mouse livers transfected with a TRIB1 overexpression, a shRNA template or a control (LacZ) adenovirus vector. The overexpression of TRIB1 reduced, whereas induction of the shRNA template increased, plasma glucose, TG, and cholesterol and simultaneously hepatic TG and glycogen levels. The involvement of TRIB1 in hepatic lipid accumulation was supported by the findings of a human SNP association study. A TRIB1 SNP, rs6982502, was identified in an enhancer sequence, modulated enhancer activity in reporter gene assays, and was significantly (P=9.39 × 10(-7)) associated with ultrasonographically diagnosed non-alcoholic fatty liver disease in a population of 5570 individuals. Transcriptome analyses of mouse livers revealed significant modulation of the gene sets involved in glycogenolysis and lipogenesis. Enforced TRIB1 expression abolished CCAAT/enhancer binding protein A (CEBPA), CEBPB, and MLXIPL proteins, whereas knockdown increased the protein level. Levels of TRIB1 expression simultaneously affected MKK4 (MAP2K4), MEK1 (MAP2K1), and ERK1/2 (MAPK1/3) protein levels and the phosphorylation of JNK, but not of ERK1/2. Pull-down and mammalian two-hybrid analyses revealed novel molecular interaction between TRIB1 and a hepatic lipogenic master regulator, MLXIPL. Co-expression of TRIB1 and CEBPA or MLXIPL reduced their protein levels and proteasome inhibitors attenuated the reduction. These data suggested that the modulation of TRIB1 expression affects hepatic lipogenesis and glycogenesis through multiple molecular interactions.