An in vitro method to investigate food effects on drug release from film-coated beads.
The influence of simulated high-fat meals on drug release from beads coated with modified-release ethylcellulose coating formulations was investigated as a function of plasticizer type and concentration, and coating level. Ethylcellulose-coated beads were soaked in peanut oil prior to testing to simulate the influence of concomitant administration of the dosage form with ingestion of fatty meals. The USP apparatus 3 dissolution procedure was employed to study the drug release properties of the beads. It was found that the ethylcellulose-coated beads plasticized with either triethyl citrate (TEC) or dibutyl sebacate (DBS) had faster drug release rates after the peanut oil treatment. Scanning electron microscopy (SEM) revealed that the peanut oil soak caused the polymeric films to detach from the surface of the bead, producing a series of uneven ridges and cracks in the coating. Modulated differential scanning calorimetry (DSC) demonstrated that the glass transition temperature was increased for DBS-plasticized films soaked in peanut oil, and that it was not influenced for TEC plasticized films. Similar results were found for the puncture strength, percent elongation, and modulus of elasticity for the DBS- and TEC-plasticized films soaked in peanut oil. The results verified that the DBS was solubilized and extracted from the plasticized film during the peanut oil soak, and that the film plasticized with the TEC was not significantly affected by the peanut oil soak. Drug release was influenced by the plasticizer type and concentration, and coating level applied to the beads.


Virulence evolution in emerging infectious diseases.
Models of virulence evolution generally consider the outcome of competition between resident and mutant parasite strains at or near endemic equilibrium. Less studied is what happens during the initial phases of invasion and adaptation. Understanding initial adaptive dynamics is particularly important in the context of emerging diseases in wildlife and humans, for which rapid and accurate intervention may be of the essence. To address the question of virulence evolution in emerging diseases, we employ a simple stochastic modeling framework. As is intuitive, the pathogen strains most likely to emerge are those with the highest net reproductive rates (R0). We find, however, that stochastic events shape the properties of emerging pathogens in sometimes unexpected ways. First, the mean virulence of emerging pathogens is expected to be larger in dense host populations and/or when transmission is high, due to less restrictive conditions for the spread of the pathogen. Second, a positive correlation between average virulence and transmissibility emerges due to a combination of drift and selection. We conclude that at least in the initial phases of adaptation, special assumptions about constraints need not be invoked to explain some virulence-transmission correlations and that virulence management practices should consider how residual variation in transmission and virulence can be selected to reduce the prevalence and/or virulence of emerging infectious diseases.


Collective in exile: Utilizing terror management theory to understand women's wailing performance.
Although women's wailing at death rites in various cultures typically amplifies mortality salience, this ritual phenomenon is absent in the research literature on terror management theory (TMT). This study explored Yemenite-Jewish wailing in Israel as an example of how a traditional performance manages death anxiety in a community context. Observations of wailing events and interviews with Yemenite-Jewish wailers and mourners in Israel were analyzed to understand respondents' perceptions of the experience of wailing as well as the anxiety-oriented psychotherapeutic expertise involved. The findings are discussed to propose an alternative outlook on the intersubjective adaptive value of death anxiety. After describing TMT's view on the role of culture in coping with death anxiety, I consider the extent to which Yemenite-Jewish wailing is consistent with the premises of TMT.


Correlates of Undernutrition in Older People in Guadeloupe (French West Indies): Results from the KASADS Study.
Objectives: This study aimed to determine the risk factors for undernutrition in community-dwelling older adults in Guadeloupe (Caribbean islands). Methods: We used data from the KArukera Study of Aging-Drugs Storage (KASADS), an observational cross-sectional study of community-dwelling older people living in Guadeloupe. The Mini Nutritional Assessment (MNA) was used to assess the risk of undernutrition. An MNA-short form (SF) score ≤11 defined the risk of undernutrition. Depression was assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, cognitive function was assessed using the Mini Mental State Examination (MMSE), frailty was assessed using the Study of Osteoporotic Fractures index (SOF), and dependency was assessed using Lawton's instrumental activities of daily living (IADL) scale. Bivariate and multivariate analyses were used to determine the correlates of undernutrition. Results: The study sample comprised 115 patients aged 65 years or older; 67.8% were women, and the mean age was 76 ± 7.8 years. The prevalence of undernutrition was 21.7% (95% CI = 15.2-30.1%). In our bivariate analysis, the risk of undernutrition was associated with MMSE score, IADL score, frailty, and CES-D score. We found no significant relation between nutrition risk and other variables, such as marital status, pain, or polypharmacy. In the multivariate analysis, the factors associated with the risk of undernutrition were MMSE score (Odd-Ratio (OR): 0.74 (0.58-0.97)) and CES-D score (OR: 1.13 (1.02-1.27)). Conclusions: Cognitive decline and the risk of depression were independently associated with the risk of undernutrition in community-dwelling older people in Guadeloupe. Although we cannot imply causality in this relation, the detection of these three key geriatric syndromes in community-dwelling elders is essential to prevent adverse health outcomes. Further studies are warranted to confirm these findings.


Self-interaction of Citrus tristeza virus p33 protein via N-terminal helix.
Citrus tristeza virus (CTV), the most economically important viral pathogen of citrus, encodes a unique protein, p33. CTV p33 shows no similarity with other known proteins, yet plays an important role in viral pathogenesis: it extends the virus host range and mediates virus ability to exclude superinfection by other variants of the virus. Previously we demonstrated that p33 is an integral membrane protein and appears to share characteristics of viral movement proteins. In this study, we show that the p33 protein self-interacts in vitro and in vivo using co-immunoprecipitation, yeast two hybrid, and bimolecular fluorescence complementation assays. Furthermore, a helix located at the N-terminus of the protein is required and sufficient for the protein self-interaction.


Early growth response gene-1 regulates the expression of the rat luteinizing hormone receptor gene.
LH receptor gene expression is primarily regulated via specific interactions of trans-acting proteins and cis-acting DNA sequences in the upstream region of the gene. In this study, we report, using luciferase assays, that the region between -171 and -137 base pairs (bp) is essential for basal expression of the rat LH receptor gene. To identify factors that interact with the region between -171 and -137 bp and regulate expression of the gene, a rat granulosa cell cDNA library was screened using a yeast one-hybrid system. A positive clone, isolated by the screening, encodes a transcription factor early growth response gene-1 (Egr-1). To determine the sequence to which Egr-1 protein binds, electrophoretic mobility shift assay (EMSA) was employed. The Egr-1 protein was produced by an in vitro transcription/translation system using a full-length rat Egr-1 cDNA. The upstream region between -171 and -137 bp contains 2 overlapping Egr-1 consensus sequences. The EMSA revealed that Egr-1 binds independently to both sites. The overexpression of Egr-1 in MA-10 cells caused an approximately 2-fold increase in reporter luciferase activity. However, no induction of the luciferase activity was observed when luciferase constructs that lacked or had mutations in either or both of the Egr-1 sites were used, indicating that Egr-1 positively regulates LH receptor gene expression. In differentiated granulosa cells that had been pretreated with FSH for 48 h, the levels of both mRNA and Egr-1 protein were induced by hCG or cAMP, reaching maximal levels approximately 1.5 h after treatment and then returning to basal levels 8 h thereafter. No Egr-1 mRNA or protein was detected in undifferentiated granulosa cells, even after stimulation with 8-bromoadenosine-cAMP. These results suggest that Egr-1 functions only in luteinized granulosa cells after stimulation with hCG or cAMP. In conclusion, the findings demonstrate that Egr-1 actually binds to the regulatory upstream region of the LH receptor gene and positively regulates receptor gene expression. In addition, Egr-1 expression was observed only in luteinized granulosa cells after stimulation with hCG or cAMP. The present study provides further support to the hypothesis that Egr-1 plays important roles in the pituitary-gonadal axis.


Effect of albumin on phenytoin and tolbutamide metabolism in human liver microsomes: an impact more than protein binding.
The cytochrome P450 (P450)-dependent conversion of phenytoin (PHT) to p-hydroxy phenytoin (pHPPH), and tolbutamide (TLB) to 4-hydroxy tolbutamide (hydroxy-TLB), in human liver microsomes was studied in the presence of increasing concentrations (0-4%) of bovine serum albumin (BSA). Therefore, the free fraction (f(u)) of PHT and TLB varied. Whereas the f(u) of PHT (5 microM) decreased, an increase (3-fold), rather than a decrease in the pHPPH formation rate was observed when BSA (<1%) was present. The stimulation was attributed to a significant decrease in apparent K(m). The change, however, was diminished as the BSA concentration reached 4% (PHT f(u) = 0.2), in which the reaction velocity remained the same as that measured in the absence of BSA. Therefore, unchanged K(m) (16.2 +/- 0.7 microM) and V(max) (9.4 +/- 0.2 pmol/min/mg of protein) values were determined based on total PHT concentrations, whereas correction for f(u) led to an unbound K(m) (K(mu)) of approximately 3.2 microM. Similarly, the metabolism of TLB (50 microM) was enhanced (approximately 2-fold) in the presence of 0.25% BSA but remained only 35% of the control activity (no BSA) at 1% BSA. However, the remaining activity was higher (3-fold) than that determined with an equivalent free concentration of TLB (4 microM) calculated according to its f(u) (0.08). The difference became less significant when BSA concentration was 4% (f(u) < 0.02). Collectively, the results suggest a 2-fold effect of BSA on PHT and TLB hydroxylation: first, facilitation of the reactions via a decrease in K(m); second, a decrease in f(u) leading to a drop in reaction rate. For a given P450 reaction, therefore, the effect of BSA may depend upon enzyme affinity, catalytic capacity, and the extent of protein binding.


Outcomes in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Via Radial Access Anticoagulated With Bivalirudin Versus Heparin: A Report From the National Cardiovascular Data Registry.
The aim of this study was to compare bivalirudin with heparin as anticoagulant agents in patients with ST-segment elevation myocardial infarction treated with radial primary percutaneous coronary intervention (PCI). Recent studies in which PCI was performed predominantly via radial access did not show bivalirudin to be superior to heparin. Outcomes were compared in patients with STEMI included in the National Cardiovascular Data Registry CathPCI database from 2009 to 2015 who underwent primary PCI via radial access and who were anticoagulated with bivalirudin or heparin. The sample included 67,368 patients, of whom 29,660 received bivalirudin and 37,708 received heparin. The 2 groups of patients did not differ significantly in their mean age or percentage of men. The unadjusted comparison showed no significant difference in the rate of the composite endpoint of death, myocardial infarction, or stroke (4.6% vs. 4.7%; p = 0.47) and a significantly higher rate of acute stent thrombosis (1.00% vs. 0.60%; p < 0.001) with bivalirudin compared with heparin. After adjusting for multiple variables, including a propensity score reflecting the probability of receiving bivalirudin, the odds ratio of the composite endpoint of death, myocardial infarction, or stroke for bivalirudin versus heparin was 0.95 (95% confidence interval: 0.87 to 1.05; p = 0.152), and the odds ratio for acute stent thrombosis was 2.11 (95% confidence interval: 1.73 to 2.57) for bivalirudin versus heparin. Major bleeding rates were not significantly different. In patients undergoing primary PCI via transradial access anticoagulated with bivalirudin or heparin, there was no difference in the composite endpoint of death, myocardial infarction, or stroke.


A potential prebiotic route to adenine from hypoxanthine.
A possible reaction mechanism for the dehydration of glycinamide (3) and N,N'-diformylurea (4) yielding hypoxanthine (2) has been investigated. Furthermore, a potential prebiotic route converting hypoxanthine (2) into adenine (1) via phosphate activation followed by substitution reaction with NH3 was studied. This reaction mimics the proposed biochemical mechanism for the conversion of IMP to AMP.


Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations.
Dermatophytosis is the most common mycosis worldwide, affecting approximately 20 to 25% of the population, regardless of gender, race, color, and age. Most antifungal agents used for the treatment of dermatophytosis belong to the azole and allylamine classes. Dermatophytes are reported to be resistant to most commercial drugs, especially microbial biofilms, in addition to their considerable toxicity. It should be emphasized the importance of looking for new molecules with reduced toxicity, as well as new targets and mechanisms of action. This work aims to incorporate nonyl 3,4-dihydroxybenzoate, a potent fungicide compound against planktonic cells and dermatophyte biofilms in nanostructured lipid systems (NLS), in order to reduce toxicity in high concentrations, improve its solubility and maintain its effectiveness. The compound was incorporated into NLS constituted by cholesterol, mixture of polyoxyethylene (23) lauryl ether (Brij®98) and soybean phosphatidylcholine (Epikuron® 200)], 2: 1 ratio and PBS (phosphate-buffered saline). The characterization of the incorporation was performed. Susceptibility tests were conducted according to document M38-A2 by CLSI (2008). The toxicity of the NLS compound was evaluated in HaCaT cell lines by the sulforhodamine B method and in alternative models Caenorhabditis elegans and zebrafish. Finally, its efficacy was evaluated against the mature Trichophyton rubrum and Trichophyton mentagrophytes biofilms. NLS and nonyl 3,4-dihydroxybenzoate loaded into NLS displayed sizes ranging from 137.8 ± 1.815 to 167.9 ± 4.070 nm; the polydispersity index (PDI) varying from 0.331 ± 0.020 to 0.377 ± 0.004 and zeta potential ranging from -1.46 ± 0.157 to -4.63 ± 0.398 mV, respectively. Polarized light microscopy results confirmed the formation of NLS of the microemulsion type. Nonyl incorporated into NLS showed minimum inhibitory concentration (MIC) values, ranging from 2 to 15.6 mg/L. The toxicity tests presented cell viability higher than 80% in all tested concentrations, as well as, a significantly increased of the survival of Caenorhabditis elegans and zebrafish models. Anti-biofilm tests proved the efficacy of the incorporation. These findings contribute significantly to the search for new antifungals and allow the systemic administration of the compound, since the incorporation can increase the solubility of non-polar compounds, improve bioavailability, effectiveness and reduce toxicity.


Mycotoxin profiles in the grain of Triticum monococcum, Triticum dicoccum and Triticum spelta after head infection with Fusarium culmorum.
The aim of study was to investigate mycotoxin profiles in the grain of spring lines of Triticum monococcum (12 lines), T. dicoccum (13 lines) and T. spelta (five lines), in comparison to the T. aestivum cultivar Sumai-3 which is resistant to Fusarium head blight. The grain was obtained from control heads and heads artificially inoculated in the field with Fusarium culmorum. Mycotoxins were determined by LC-MS/MS. A total of 11 toxins were identified in control grain samples. Deoxynivalenol (DON) concentrations exceeded 0.5 mg kg(-1) in only three samples of T. monococcum grain and in one sample of T. dicoccum grain. Inoculation with F. culmorum resulted in a substantial increase in the concentrations of DON (to 63 mg kg(-1)) in the T. monococcum and DON-3-glucoside (to 5.6 mg kg(-1)) in the T. dicoccum. Inoculation contributed to a drop in tentoxin levels (by 57% in T. spelta) and to an increase of cyclodepsipeptide concentrations (in particular enniatins B and B(1)) being two-fold (T. monococcum) to four-fold (T. dicoccum) higher on average than in control samples. The Sumai-3 responded to inoculation with nearly a two-fold drop in the levels of the cyclodepsipeptides. The results of a discriminant analysis for all identified toxins indicate that einkorn, emmer and spelt differ significantly with regard to the mycotoxin profiles of their grain.


Structure of the human PKD1-PKD2 complex.
Mutations in two genes, PKD1 and PKD2, account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo-electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five-transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins.


Synaptic transmission and recognition memory: time course of changes in N-methyl-D-aspartate receptors after imprinting.
Previous studies have shown that a restricted region of the chick forebrain (the intermediate and medial parts of the hyperstriatum ventrale, IMHV) is crucial for the learning process of imprinting. A learning-related increase in N-methyl-D-aspartate (NMDA) receptor binding has previously been shown in the left IMHV 8.5 hr after training with an imprinting stimulus. The present experiments showed that this increase in binding in the left IMHV does not occur until 6-8.5 hr after training: There was no significant change in binding in either the left or right IMHV less than 0.5, 3, or 6 hr after training. No significant change in binding occurred in the right IMHV 8.5 hr after training. It is probable that the increase in binding in the left IMHV is associated with the recognition memory of imprinting.


Selective removal of toxic Cr(VI) from aqueous solution by adsorption combined with reduction at a magnetic nanocomposite surface.
The adsorption of toxic hexavalent chromium (Cr(VI)) and its reduction to trivalent chromium (Cr(III)) are important processes for the treatment of industrial wastewater. Conducting polymers can adsorb and reduce Cr(VI) to less toxic Cr(III) but have low adsorption capacities due to agglomeration of particles and are difficult to separate from treated water. In this study, magnetic polypyrrole (PPy)-polyaniline (PANI)/iron oxide (Fe3O4) nanocomposite was synthesized for the selective removal of Cr(VI) in aqueous solution. PPy-PANI/Fe3O4 nanocomposite was characterized using various techniques including ATR-FTIR, FE-SEM, HR-TEM, EDX, TGA, XRD, VSM and XPS analyses. PPy-PANI/Fe3O4 nanocomposite (0.05g) removed 99% of Cr(VI) from aqueous solution (100mg/L, pH 2). Speciation studies confirmed Cr(VI) adsorption and reduction to Cr(III) by the PPy-PANI/Fe3O4 nanocomposite in solutions with initial pH of 2 and 3 and that no Cr(VI) reduction occurred at pH values of 4 and above. The Langmuir maximum adsorption capacity for Cr(VI) removal by PPy-PANI/Fe3O4 nanocomposite at pH 2 was 303mg/g at 25°C. PPy-PANI/Fe3O4 nanocomposite was highly selective for Cr(VI) removal and could be used for three consecutive treatment cycles without loss of adsorption capacity. Moreover, the magnetic nanocomposite could be separated from the reaction fluid using an external magnet. PPy-PANI/Fe3O4 nanocomposite is therefore a promising magnetic adsorbent for the treatment of industrial wastewater.


Ribosomal Stalling During Translation: Providing Substrates for Ribosome-Associated Protein Quality Control.
Cells of all organisms survey problems during translation elongation, which may happen as a consequence of mRNA aberrations, inefficient decoding, or other sources. In eukaryotes, ribosome-associated quality control (RQC) senses elongation-stalled ribosomes and promotes dissociation of ribosomal subunits. This so-called ribosomal rescue releases the mRNA for degradation and allows 40S subunits to be recycled for new rounds of translation. However, the nascent polypeptide chains remain linked to tRNA and associated with the rescued 60S subunits. As a final critical step in this pathway, the Ltn1/Listerin E3 ligase subunit of the RQC complex (RQCc) ubiquitylates the nascent chain, which promotes clearance of the 60S subunit while simultaneously marking the nascent chain for elimination. Here we review the ribosomal stalling and rescue steps upstream of the RQCc, where one witnesses intersection with cellular machineries implicated in translation elongation, translation termination, ribosomal subunit recycling, and mRNA quality control. We emphasize both recent progress and future directions in this area, as well as examples linking ribosomal rescue with the production of Ltn1-RQCc substrates.


[Tryptase levels are elevated during spontaneous ischemic episodes in unstable angina but not after the ergonovine test in variant angina].
Activated mast cells are present in human coronary atheromas, as well as in the adventitia of patients with variant angina, and may play an important role in plaque rupture and coronary vasomotion. To assess whether or not activation of mast cells is a primary event, we measured serum levels of tryptase, a specific marker of mast cell activation, in 8 patients with unstable angina during a spontaneous ischemic episode (Group 1) and in 5 patients with variant angina (Group 2) during ergonovine-induced coronary spasm. Blood samples were collected as soon as possible after the onset of pain and ECG changes (0 min), and after 5, 15 and 60 min. Tryptase levels in Group 1 were 0.13 U/l (range 0.017-0.44) at the onset of pain and significantly raised to 0.75 U/l (range 0.05-2.49) at 5 min, decreasing to 0.076 U/l (range 0.018-0.16) at 15 min and to 0.085 U/l (range 0.01-0.25) at 60 min (p = 0.035). Conversely, tryptase levels in Group 2 were 0.09 U/l (range 0.07-0.13) at 0 min, 0.11 U/l (range 0.07-0.22) at 5 min, 0.10 U/l (range 0.07-0.18) at 15 min, 0.11 U/l (range 0.07-0.17) at 60 min (NS). In conclusion, tryptase levels raise during spontaneous ischemic episodes in unstable angina, but not after ergonovine-provoked ischemia in variant angina, suggesting that a primary, yet unknown stimulus, may activate mast cells during some ischemic episodes in unstable angina.


Concurrent Deficiency of Factor V and Factor VIII in a Pediatric Patient: A Case Report.
This case report delves into an uncommon coagulopathy recognized as factor V and VIII deficiency (F5F8D), which follows an autosomal recessive inheritance pattern. The focal point of this study is a five-year-old Asian female who was initially presented with complaints of hematuria, epistaxis, and bruises all over the body. Comprehensive haematological and coagulation profiling unveiled indicators such as diminished haemoglobin levels and prolonged activated partial thromboplastin time (aPTT), prothrombin time (PT), and international normalized ratio (INR). Subsequent factor assays demonstrated noteworthy reductions in both factor V and factor VIII activities, unequivocally confirming the existence of a concurrent deficiency in these crucial factors. Notably, patients exhibiting elongated INR, PT, and aPTT values necessitate a comprehensive assessment for potential combined deficits in factors V and VIII when formulating a differential diagnosis. In cases where substantial bleeding manifestations are evident during the patient's presentation, it is prudent to exercise judicious medical management strategies.


The Difficult Evolution of Intensive Cardiac Care Units: An Overview of the BLITZ-3 Registry and Other Italian Surveys.
Coronary care units, initially developed to treat acute myocardial infarction, have moved to the care of a broader population of acute cardiac patients and are currently defined as Intensive Cardiac Care Units (ICCUs). However, very limited data are available on such evolution. Since 2008, in Italy, several surveys have been designed to assess ICCUs' activities. The largest and most comprehensive of these, the BLITZ-3 Registry, observed that patients admitted are mainly elderly males and suffer from several comorbidities. Direct admission to ICCUs through the Emergency Medical System was rather rare. Acute coronary syndromes (ACS) account for more than half of the discharge diagnoses. However, numbers of acute heart failure (AHF) admissions are substantial. Interestingly, age, resources availability, and networking have a strong influence on ICCUs' epidemiology and activities. In fact, while patients with ACS concentrate in ICCUs with interventional capabilities, older patients with AHF or non-ACS, non-AHF cardiac diseases prevail in peripheral ICCUs. In conclusion, although ACS is still the core business of ICCUs, aging, comorbidities, increasing numbers of non-ACS, technological improvements, and resources availability have had substantial effects on epidemiology and activities of ICCUs. The Italian surveys confirm these changes and call for a substantial update of ICCUs' organization and competences.


Being diagnosed with cancer: The experiences of patients with non-Hodgkin's lymphoma.
To explore the lived experiences of patients on receiving a diagnosis of non-Hodgkin's lymphoma. Persons with non-Hodgkin's lymphoma are often diagnosed with cancer when at an advanced stage. This may arise due to a lack of screening programmes and delays in help seeking as the symptoms experienced are fairly nonspecific in nature. Consequently, receiving an unexpected diagnosis of non-Hodgkin's lymphoma may pose a psychosocial challenge to the individual. An exploratory qualitative phenomenological design was used. Six adult patients diagnosed with non-Hodgkin's lymphoma were recruited and participated in two semi-structured interviews at different timepoints. Transcribed texts were analysed using interpretative phenomenological analysis. Three main themes emerged: "Emotional reaction to the diagnosis," "Struggling with a lack of understanding" and "Searching through past experiences." Most of the participants expressed shock, disbelief and fear at the news of being diagnosed with non-Hodgkin's lymphoma. A sense of relief was expressed by one participant, who could now provide a label to the pain experienced. This study highlights the responses of patients with non-Hodgkin's lymphoma on receiving a diagnosis. These responses are influenced by their knowledge about the illness, type of symptoms experienced, their own personal circumstances and the manner in which the diagnosis was given. Nursing care relates to an understanding of the patients' experiences. By reflecting on these findings, nurses are empowered to communicate with persons who have received a diagnosis of non-Hodgkin's lymphoma in a patient-sensitive manner, which establishes a relationship of trust and respect.


Copper-independent lysosomal localisation of the Wilson disease protein ATP7B.
In hepatocytes, the Wilson disease protein ATP7B resides on the trans-Golgi network (TGN) and traffics to peripheral lysosomes to export excess intracellular copper through lysosomal exocytosis. We found that in basal copper or even upon copper chelation, a significant amount of ATP7B persists in the endolysosomal compartment of hepatocytes but not in non-hepatic cells. These ATP7B-harbouring lysosomes lie in close proximity of ~10 nm to the TGN. ATP7B constitutively distributes itself between the sub-domain of the TGN with a lower pH and the TGN-proximal lysosomal compartments. The presence of ATP7B on TGN-lysosome colocalising sites upon Golgi disruption suggested a possible exchange of ATP7B directly between the TGN and its proximal lysosomes. Manipulating lysosomal positioning significantly alters the localisation of ATP7B in the cell. Contrary to previous understanding, we found that upon copper chelation in a copper-replete hepatocyte, ATP7B is not retrieved back to TGN from peripheral lysosomes; rather, ATP7B recycles to these TGN-proximal lysosomes to initiate the next cycle of copper transport. We report a hitherto unknown copper-independent lysosomal localisation of ATP7B and the importance of TGN-proximal lysosomes but not TGN as the terminal acceptor organelle of ATP7B in its retrograde pathway.


An apoptosis-associated mammary protein deficiency leads to enhanced production of IgM antibodies against multiple damage-associated molecules.
Milk fat globule epidermal growth factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and enhances the engulfment of apoptotic cells by macrophages. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in the MFG-E8-deficient (MFG-E8(-/-)) mice, and these mice develop an autoimmune disease resembling human systemic lupus erythematosus. We found that the MFG-E8 deficiency was accompanied by the increased production of immunoglobulins. Further Western blot and ELISA analyses validated the increase in the IgM levels in the MFG-E8(-/-) mice. It was also revealed that the sera from the MFG-E8(-/-) mice cross-reacted with oxidation-specific epitopes generated upon incubation of serum albumin with the peroxidized lipids. Among the modified proteins with several unsaturated aldehydes of chain lengths varying from three to nine carbons, the MFG-E8(-/-) mice sera exclusively cross-reacted with the protein-bound 4-oxo-2-nonenal (ONE), a highly reactive aldehyde originating from the peroxidation of ω6 polyunsaturated fatty acids. In addition, the IgM monoclonal antibodies (mAbs) that selectively cross-reacted with the ONE-modified proteins were generated from the MFG-E8(-/-) mice. A subset of the ONE-specific IgM mAbs significantly recognized the late apoptotic and necrotic cells and enhanced the phagocytosis by macrophages. These data demonstrate that the impairment of the phagocytic clearance of apoptotic cells through MFG-E8 can lead to the generation of natural antibodies, which may play a critical role in removing multiple damage-associated molecules, including oxidation-specific epitopes and late apoptotic/necrotic cells.


Flagellin gene polymorphism analysis of Campylobacter jejuni infecting man and other hosts and comparison with biotyping and somatic antigen serotyping.
Flagellin gene sequence polymorphisms were used to discriminate amongst 77 strains of Campylobacter jejuni from sporadic and outbreak-associated human enteric infections, and from chickens, sheep and calves. The results were assessed in relation to Lior biotyping and serotyping (Penner somatic antigens). Eight DNA PCR-RFLP patterns (genotypes) were identified by analysis of HinfI fragment length polymorphisms in flagellin gene (flaA) polymerase chain reaction (PCR) products. One genotype (F-1) was a feature of 55% of strains. Strains within the genotypes were heterogeneous with respect to somatic antigens with 12 serogroups represented amongst the C. jejuni isolates of flaA type F-1. Serogroups Pen 1, 2 and 23 were the commonest (45%) amongst the 20 different serogroups represented. Several unique clusters of isolates with diverse biotypes were defined, and one cluster (F-7/Pen 23) contained epidemiologically implicated outbreak strains as well as sheep and calf isolates. We conclude that HinfI flaA typing is reproducible and offers high typability, and its combination with serogrouping provides a novel approach to characterizing isolates of C. jejuni with improved discrimination.


Frequent emergency department utilization and behavioral health diagnoses.
There are 12 million emergency department (ED) visits each year related to behavioral health diagnoses. Frequent ED utilization among subpopulations, such as those with behavioral health diagnoses, flags the need for more accessible and effective healthcare delivery systems. Reducing frequent ED use is essential to controlling healthcare cost and poor outcomes of ED overcrowding. The purpose of this study is to stratify individuals by overall health complexity and examine the relationship of behavioral health diagnoses (psychiatric and substance abuse) as well as frequent treat-and-release ED utilization in a cohort of Medicaid recipients. This study was a retrospective analysis of 2009 Medicaid claims from two Western New York State counties. The claims represented 56,491 individuals (18-64 years old). Individuals were stratified into four separate cohorts for analysis based on underlying disease complexity. Data were analyzed using logistic regression models. The following factors significantly increased the odds of frequent treat-and-release ED use in all the four complexity cohorts: psychiatric diagnosis (ORs = 1.4-2.3), substance abuse (ORs = 2.4-3.8), and smoking (ORs = 1.7-4.0). Medicaid patients with behavioral health diagnoses show high risk of frequent treat-and-release ED use. The results of this study show that psychiatric diagnosis, substance abuse, and smoking are associated with increased odds of frequent treat-and-release ED utilization for Medicaid recipients in all categories of underlying disease complexity. Our findings support associations reported in the literature.


New Continuous Barbed Suture Device with Stratafix for the Vaginal Stump in Laparoscopic Hysterectomy.
Closure of the vaginal stump in total laparoscopic hysterectomy (TLH) performed by interrupted suture is time-consuming and requires sufficient experience. Stratafix (SF) is a new type of antibacterial monofilament absorbable suture which has multiple small anchors on the string surface. There is no information concerning the efficacy of SF for vaginal stump suture in minimally invasive hysterectomy. We retrospectively evaluated the operative complications and SF (n = 20) advantages for the vaginal stump in TLH and compared with a cohort of patients with conventional sutures (n = 20). The differences in performance based on operators' skill levels were also considered. The time taken to close vaginal stump in the SF suture group was significantly lower than the conventional group (median times: 13.1 vs. 18.0 min, respectively; P = 0.038). Closure by a less experienced operator using SF suture was reduced by 7.2 min. The junior operator median vaginal suture time was only 2.6 min longer than the senior operator median time in SF suture group (P = 0.218), whereas an 8.4 min difference was recorded in the conventional suture group (P = 0.043). Total operation times did not significantly correlate with vaginal suturing techniques (median times: 126 vs. 145 min, respectively; P = 0.718). Complications regarding the vaginal stump closure techniques including organ injury, bleeding, wound separation, and pain did not occur in both groups. SF suturing facilitates the vaginal stump closure in TLH without increasing the complications. SF allowed vaginal stump approximation and reduced the operative burden, especially in less experienced operators.


A Phosphorylatable Sphingosine Analog Induces Airway Smooth Muscle Cytostasis and Reverses Airway Hyperresponsiveness in Experimental Asthma.
In asthma, excessive bronchial narrowing associated with thickening of the airway smooth muscle (ASM) causes respiratory distress. Numerous pharmacological agents prevent experimental airway hyperresponsiveness (AHR) when delivered prophylactically. However, most fail to resolve this feature after disease is instated. Although sphingosine analogs are primarily perceived as immune modulators with the ability to prevent experimental asthma, they also influence processes associated with tissue atrophy, supporting the hypothesis that they could interfere with mechanisms sustaining pre-established AHR. We thus assessed the ability of a sphingosine analog (AAL-R) to reverse AHR in a chronic model of asthma. We dissected the pharmacological mechanism of this class of agents using the non-phosphorylatable chiral isomer AAL-S and the pre-phosphorylated form of AAL-R (AFD-R) in vivo and in human ASM cells. We found that a therapeutic course of AAL-R reversed experimental AHR in the methacholine challenge test, which was not replicated by dexamethasone or the non-phosphorylatable isomer AAL-S. AAL-R efficiently interfered with ASM cell proliferation in vitro, supporting the concept that immunomodulation is not necessary to interfere with cellular mechanisms sustaining AHR. Moreover, the sphingosine-1-phosphate lyase inhibitor SM4 and the sphingosine-1-phosphate receptor antagonist VPC23019 failed to inhibit proliferation, indicating that intracellular accumulation of sphingosine-1-phosphate or interference with cell surface S1P1/S1P3 activation, are not sufficient to induce cytostasis. Potent AAL-R-induced cytostasis specifically related to its ability to induce intracellular AFD-R accumulation. Thus, a sphingosine analog that possesses the ability to be phosphorylated in situ interferes with cellular mechanisms that beget AHR.


Proteomic Signatures of Healthy Intervertebral Discs From Organ Donors: A Comparison With Previous Studies on Discs From Scoliosis, Animals, and Trauma.
To catalog and characterize the proteome of normal human intervertebral disc (IVD). Nine magnetic resonance imaging (MRI) normal IVDs were harvested from 9 different brain dead yet alive voluntary organ donors and were subjected to electrospray ionization-liquid chromatography tandem mass spectrometry (ESI-LC-MS/MS) acquisition. A total of 1,116 proteins were identified. Functional enrichment analysis tool DAVID ver. 6.8 categorized: extracellular proteins (38%), intracellular (31%), protein-containing complex (13%), organelle (9%), membrane proteins (6%), supramolecular complex (2%), and 1% in the cell junction. Molecular function revealed: binding activity (42%), catalytic activity (31%), regulatory activity (14%), and structural activity (7%). Molecular transducer, transporter, and transcription regulator activity together contributed to 6%. A comparison of the proteins obtained from this study to others in the literature showed a wide variation in content with only 3% of bovine, 5% of murine, 54% of human scoliotic discs, and 10.2% of discs adjacent to lumbar burst fractures common to our study of organ donors. Between proteins reported in scoliosis and lumbar fracture patients, only 13.51% were common, further signifying the contrast amongst the various MRI normal IVD samples. The proteome of "healthy" human IVDs has been defined, and our results show that proteomic data on IVDs obtained from scoliosis, fracture patients, and cadavers lack normal physiological conditions and should not be used as biological controls despite normal MRI findings. This questions the validity of previous studies that have used such discs as controls for analyzing the pathomechanisms of disc degeneration.


Evaluation of Statin Eligibility, Prescribing Practices, and Therapeutic Responses Using ATP III, ACC/AHA, and NLA Dyslipidemia Treatment Guidelines in a Large Urban Cohort of HIV-Infected Outpatients.
Statin coverage has been examined among HIV-infected patients using Adult Treatment Panel III (ATP III) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines, although not with newer National Lipid Association (NLA) guidelines. We investigated statin eligibility, prescribing practices, and therapeutic responses using these three guidelines. Sociodemographic, clinical, and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients enrolled in the DC Cohort, a multi-center, prospective, observational study in Washington, DC. This analysis included patients aged ≥21 years receiving primary care at their HIV clinic site with ≥1 cholesterol result available. Of 3312 patients (median age 52; 79% black), 52% were eligible for statins based on ≥1 guideline, including 45% (NLA), 40% (ACC/AHA), and 30% (ATP III). Using each guideline, 49% (NLA), 56% (ACC/AHA), and 73% (ATP III) of eligible patients were prescribed statins. Predictors of new prescriptions included older age (aHR = 1.16 [1.08-1.26]/5 years), body mass index ≥30 (aHR = 1.50 [1.07-2.11]), and diabetes (aHR = 1.35 [1.03-1.79]). Hepatitis C coinfection was inversely associated with statin prescriptions (aHR = 0.67 [0.45-1.00]). Among 216 patients with available cholesterol results pre-/post-prescription, 53% achieved their NLA cholesterol goal after 6 months. Hepatitis C coinfection was positively associated (aHR = 1.87 [1.06-3.32]), and depression (aHR = 0.56 [0.35-0.92]) and protease inhibitor use (aHR = 0.61 [0.40-0.93]) were inversely associated, with NLA goal achievement. Half of patients were eligible for statins based on current US guidelines, with the highest proportion eligible based on NLA guidelines, yet, fewer received prescriptions and achieved treatment goals. Greater compliance with recommended statin prescribing practices may reduce cardiovascular disease risk among HIV-infected individuals.


Ultraviolet radiation and incidence of cataracts in a nationwide US cohort.
We examine the risk of cataract and cataract surgery with measures of ultraviolet radiation (UVR) exposure and UVR sensitivity in a large, nationwide population of indoor workers. Participants from the US Radiologic Technologists Study were followed from age at baseline survey (2003-2005) to age at earliest of cataract diagnosis, cataract surgery, or completion of last survey (2012-2013). UVR-related factors included satellite-based ambient UVR linked to lifetime residences, time spent outdoors across various age periods, history of blistering sunburns, prior diagnosis of keratinocyte carcinoma, and iris color. We used Cox proportional hazards models with age as timescale to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for cataract and cataract surgery. Participants had a median age of entry of 54.0 years, were 80.0% female, and 95.7% white. Of the 44, 891 eligible participants, 9399 cases of cataract and 3826 cases of cataract surgery were reported. Ambient UVR (quintile 5 vs. 1) was associated with an increased risk of cataract (HR = 1.08; 95% CI: 1.01-1.16) and cataract surgery (HR = 1.16; 95% CI: 1.05-1.29). Lifetime average time spent outdoors was not associated with cataract risk. History of blistering sunburns before and after age 15, but not previous keratinocyte carcinoma diagnosis was associated with both cataract and cataract surgery. Our results suggest a modest role for residence-based ambient UVR and cataract risk among indoor workers in the United States.


Identification of a DNA Aptamer That Binds to Human Monocytes and Macrophages.
As cancer strategies shift toward immunotherapy, the need for new binding ligands to target and isolate specific immune cell populations has soared. Based on prior work identifying a peptide specific for murine M2-like macrophages, we sought to identify an aptamer that could bind human M2-like macrophages. Tumor-associated macrophages (TAMs) adopt an M2-like phenotype and support tumor progression and dissemination. Here, we employed cell-SELEX to identify an aptamer ligand that targets this cell population over tissue resident (M0-like) or tumoricidal (M1-like) macrophages. Instead, we identified an aptamer that binds both human M0- and M2-like macrophages and monocytes, with highest binding affinity to M2-like macrophage (Kd ∼ 20 nM) and monocytes (Kd ∼ 45 nM) and minimal binding to other leukocytes. The aptamer binds to CD14+ but not CD16+ monocytes, and is rapidly internalized by these cells. We also demonstrate that this aptamer is able to bind human monocytes when both are administered in vivo to mice. Thus, binding to these cell populations (monocytes, M0-like and M2-like macrophages), this aptamer lends itself toward monocyte-specific applications, such as monocyte-targeted drug delivery or column selection.


Bone Reduction to Facilitate Immediate Implant Placement and Loading Using CAD/CAM Surgical Guides for Patients With Terminal Dentition.
The aim of this study is to present a method, using 3 computer-aided design/computer-aided manufacturing (CAD/CAM) surgical guides, to accurately obtain the desired bone reduction followed by immediate implant placements and loading for patients diagnosed with terminal dentition. Patients who had bone reduction, implants placed, and immediate loading using Anatomage Invivo 5 CAD/CAM surgical guides between the period 2013 and 2015 were evaluated retrospectively. Patients diagnosed with terminal dentition and treated using the "3-guide technique" were identified. Pre- and postsurgical images were superimposed to evaluate deviations of the bone reduction and deviations at the crest, apex, and angle of implants placed. Twenty-six implants placed in 5 patients were included in this study. The overall deviation means measured for bone reduction was 1.98 mm. The overall deviation means measured for implant placement at the crest, apex, and angle were 1.43 mm, 1.90 mm, and 4.14°, respectively. The CAD/CAM surgical guide fabrication is an emerging tool that may facilitate the surgical process and aid in safe and predictable execution of bone reduction and immediate implant placement. Using 3 CAD/CAM surgical guides, a method is presented to obtain the desired bone reduction followed by immediate implant placement and loading for patients diagnosed with terminal dentition. This method may improve guide stability for patients with terminal dentition undergoing complete implant-supported treatment by taking advantage of the teeth to be extracted.


Effect of supplementation with rumen-protected choline and green tea extract on production performance of transition Karan Fries cows.
The main objective of this study was to estimate the effect of supplementation of rumen-protected choline (RPC) and green tea extract (GTE) on production parameters in transition Karan Fries (KF) cows. The present experiment was carried out on 32 pregnant KF cows. In the control group, cows were fed basal diet. In T1, each cow was fed RPC (55 g/day), in T2 - GTE (3 g/d), and in T3- RPC + GTE (55+3) g/day along with basal diet. The duration of the experiment was 30 days before calving to 60 days after parturition. Feeding of both RPC and GTE significantly increased milk yield (p≤0.01), 4% fat corrected milk yield (p≤0.01), milk fat (p≤0.01), and total solid content (p≤0.05) than control. There was no significant difference (p≥0.05) in milk protein, lactose, and solids not fat (SNF) content among the groups. Supplementing RPC and GTE in combination improved milk yield and fat content of the milk without altering protein, lactose content of the milk in transition KF cows.


Arthropathies and thyroid diseases.
Improvement of articular symptoms following thyroidectomy has often been observed in patients with an association of thyroid and joint diseases. An assessment has therefore been made of the types of arthropathy thus benefited and the anatomopathological features of the thyroid in patients with concomitant joint diseases. An account is given of the arthropathies associated with nontoxic nodular goitre (NTG). Three cell markers are examined to identify immunocytokine elements differentiating thyroid diseases. Immunohistochemical examination shows extravasal lymphocyte infiltrates; thyrocytes were negative for HLA-Cl II, CD38 and IL-6R, and only dim-positive for HLA-Cl I. Endothelial cells were positive for HLA-Cl I and II and CD38, and negative for IL-6R. The lymphocyte were positive for HLA-Cl I, HLA-Cl II and CD38, but negative for IL-6R. The follow-up of 6 thyroidectomised patients disclosed improvement in joint pain and remission of rheumatoid arthritis and spondylarthritis. Association of nodular goitre with arthro-pathies is demonstrated. Arthritis and arthralgia are frequent in patients with thyroid diseases, we particularly found the association with MHNG and Hurthle cell adenoma. Arthritis and arthralgia quickly improve after thyroidectomy. Immunohistochemical NTG thyrocytes are still normal cells (HLA-Cl II negative) by contrast with their HLA-Cl II positivity in autoimmune thyroiditis.


Pleural Effusion or Main Left Bronchus Mucus Obstruction: To Drain or Not to Drain? Decision-Making for Young Surgeon on Call.
Mucous plugs occur in a number of pulmonary conditions. Central right or left bronchus mucus plug causes complete pulmonary collapse making it an emergency life-threatening case. We describe the case of an 80-year-old man that, in postoperative period after a urological intervention, has had a progressive tachypnea and dyspnea during hospitalization for urological problems. Young surgeon on call was called.


Improving the appropriateness of laboratory submissions for urinalysis from general practice.
Urine is the most common microbiology laboratory specimen. Submissions increase annually by 5-10%, and many specimens may be unnecessary. To assess the impact of guidance, implemented by interactive workshops and reinforced with modified request forms, on specimen submission. This was a prospective randomized controlled study with modified Zelen design. The study population comprised five primary care trusts (PCTs) in Gloucestershire/County Durham/Darlington, containing 82 general practices in six geographical clusters. The six clusters were randomly assigned to urine workshop covering submission in the elderly, adults and children or a control workshop. Within these groups, half the practices were randomized to receive modified laboratory forms emphasizing the workshop messages. Practices were not aware of the study. Workshops lead to a 12% reduction in urine submissions from 16- to 64-year olds, which persisted for the 15 months but had no effect on bacteriuria rate. Workshops had no significant effect in the elderly or children. Modified forms were not associated with any reduction in submissions but were associated with an 11% reduction in detection of significant bacteriuria in 16- to 64-year olds. The 12% decrease in urine submissions from 16- to 64-year olds, attained with workshops, may help counter relentlessly rising test submissions. Modified forms are currently not worth pursuing. When educational workshops are used across PCTs to change practice, the change in test submission is smaller than attained in educational initiatives involving volunteers. Workshops may be more effective if they also discuss urine submissions from asymptomatic patients and are directed at high testing practices and care homes.


Lymphocele after renal transplantation: a case report.
A case of lymphocele after an allograft renal transplant at the National Taiwan University Hospital is reported. A 32-year-old female patient received a kidney transplant from a cadaver donor on 23 November 1990 after a 10-year course of hemodialysis. Acute tubular necrosis of 31 days duration developed on the 6th postoperative day after a severe episode of acute rejection. On the 44th POD, sonographic examination showed an echo-free space between the graft and the urinary bladder. Emergent marsupialization through an intraperitoneal window of the lymphocele was performed on the 45th POD due to a sudden decrease in urine output. After releasing the compression of the lymphocele, the urine output returned to over 2,500 mL on the following day. The patient was discharged on the 63rd POD with normal renal function. Repeated sonographic examination showed no reaccumulation of lymphocele. The literature concerning lymphocele is reviewed.


Serum Folate Levels and Lung Cancer Risk: A Meta- Epidemiological Study of Population-based Case-Control Studies.
While it has been claimed that lung cancer occurs due to epigenetic mechanisms, four systematic reviews were reported to investigate the association between serum folate levels and lung cancer risk. Considering some methodological problems founded in the systematic review, a meta-epidemiological study was conducted. The selection criteria of this study were defined that a case-control study was conducted to determine the risk of lung cancer occurrence according to the concentration of serum folate and its results showed odds ratio and its 95% confidence interval. Additional paper was explored from cited lists of 4 papers selected by previous systematic reviews. Random effect model was applied if I-squared value was over 50%. For 5 case-control studies selected, the summary odds ratios (and their 95% confidence intervals) were 0.82 (0.74-0.90) in men, 0.70 (0.62-0.79) in former smokers, and 0.86 (0.75-1.00) in non-smokers. Higher foliate levels can decrease lung cancer risk in men and former smokers. Especially, the protective effect was highest in former smokers compared in non-smokers and current smokers. Based on these facts, folate fortification programs to reduce lung cancer risk would be focused on former smokers in men. And some epidemiological studies are needed to provide a hypothesis to explain the sex differences in the association between folate and lung cancer risk.


Site-specific, insertional inactivation of incA in Chlamydia trachomatis using a group II intron.
Chlamydia trachomatis is an obligate, intracellular bacterial pathogen that has until more recently remained recalcitrant to genetic manipulation. However, the field still remains hindered by the absence of tools to create selectable, targeted chromosomal mutations. Previous work with mobile group II introns demonstrated that they can be retargeted by altering DNA sequences within the intron's substrate recognition region to create site-specific gene insertions. This platform (marketed as TargeTron™, Sigma) has been successfully employed in a variety of bacteria. We subsequently modified TargeTron™ for use in C. trachomatis and as proof of principle used our system to insertionally inactivate incA, a chromosomal gene encoding a protein required for homotypic fusion of chlamydial inclusions. C. trachomatis incA::GII(bla) mutants were selected with ampicillin and plaque purified clones were then isolated for genotypic and phenotypic analysis. PCR, Southern blotting, and DNA sequencing verified proper GII(bla) insertion, while continuous passaging in the absence of selection demonstrated that the insertion was stable. As seen with naturally occurring IncA(-) mutants, light and immunofluorescence microscopy confirmed the presence of non-fusogenic inclusions in cells infected with the incA::GII(bla) mutants at a multiplicity of infection greater than one. Lack of IncA production by mutant clones was further confirmed by Western blotting. Ultimately, the ease of retargeting the intron, ability to select for mutants, and intron stability in the absence of selection makes this method a powerful addition to the growing chlamydial molecular toolbox.


Cardiovascular pathology in osteogenesis imperfecta type IIA with a review of the literature.
Lethal perinatal osteogenesis imperfecta (OI Type II) is a biochemically diverse collagen disorder characterized by short, crumpled long bones, beaded ribs, blue sclerae and thin, fragile skin. Cardiovascular abnormalities are rarely described. Using morphometry and light and electron (SEM and TEM) microscopy, we analyzed the hearts and great vessels from 2 fetuses with OI Type IIA and compared the findings with age-matched controls. The heart weights and atrioventricular valve (AVV) circumferences were reduced in OI. The chordae tendineae were short and fragile; both the AVVs and the chordae tendineae were hypercellular. TEM showed relatively little organized collagen in the chordae tendineae of OI fetuses. Furthermore, quantitative evaluation of collagen fibril size revealed a decrease in the cross-sectional diameter. There was also a marked decrease in the adventitial and intramural collagen of the intramyocardial arteries and great vessels in OI. Our study reports, for the first time, specific lesions in the cardiovascular systems of patients with OI Type II and reviews the cardiovascular pathology in other forms of OI.


Short-term exposure to air pollution and inflammation-sensitive biomarkers.
To evaluate the effect of short-term exposure to air pollutants on inflammation-sensitive biomarkers in apparently healthy individuals. We enrolled all participants from The Tel-Aviv Sourasky Medical Center inflammation survey held between 2003 and 2006, excluding participants with an acute or chronic inflammatory disease, pregnancy, steroidal or nonsteroidal treatment, or a recent invasive procedure. Additional subjects were excluded for living more than 11km from the nearest air pollution monitoring station. Analysis was performed separately for men and women. Linear regression models were fitted for each inflammatory variable against air pollutant variables (particulate matter under 10microm, sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone) for increasing lag times of up to 7 days, and adjusted for all possible and known confounding parameters. The study population comprised 3659 individuals (2203 males and 1456 females). We found a statistically significant negative correlation in the male population between air pollutants, mainly NO2, SO2, and CO, and fibrinogen in several lag days. A positive correlation was found for PM10 at day 7. No such correlation was found for CRP and WBC, or for the female population. Our findings do not support the potential link between short-term exposure to air pollution and enhanced inflammation as a possible explanation for increased cardiovascular morbidity. Additional large-scale population-based studies with good methodological design are needed in order to clarify this issue.


Ultrasonographic evaluation of parathyroid hyperplasia in dialysis patients.
Secondary hyperparathyroidism (SHPT) is one of the most common complications in patients with chronic kidney disease (CKD). Bone and mineral disorders, increased morbidity and mortality are the consequences of SHPT. Therefore, prevention and control of hyperparathyroidism is one of the main objectives in the management of patients with CKD, particularly in dialysis patients. It is well known that SHPT in CKD is not only a state of increased parathyroid hormone (PTH) synthesis and secretion, but more importantly, it is a state of parathyroid gland (PTG) hyperplasia. The serum concentration of intact PTH is the main method used to assess PTG overactivity. Unfortunately, estimating the size and shape of the PTG in SHPT diagnosis, i.e., parathyroid hyperplasia, is still neglected. Among the various procedures, ultrasonography could be the method of choice to detect PTG size and shape because of its simplicity and noninvasiveness. This method can be sufficiently sensitive to distinguish diffuse and nodular hyperplasia.


Contextual determinants of subjective age in midlife and old age: The example of daily variations in COVID-19 infection rates.
Feeling younger than one's age reflects a process of age-group dissociation that is frequently activated when belonging to one's age group has negative connotations. Regarding the Corona pandemic, time periods with a higher number of individuals infected with coronavirus disease (COVID-19) might have elicited younger subjective ages, particularly among older adults as they belonged to a "COVID-19 risk group." We investigated the subjective age of n = 233 German individuals aged 47-94 years who were assessed between June and September 2020. COVID-19 cases in Germany were considerably rising from August 2020 on. We were able to confirm an association between a higher infection rate and a younger subjective age; individuals assessed in June, July, August, and September felt on average 9.2%, 9.6%, 13.2%, and 19.2% younger than their chronological age. Controlling for subjective age assessed prior to the pandemic, current depressive symptoms and health concerns, as well as for age, gender, and education, the effect of month of assessment on subjective age remained significant. Also, the number of new COVID-19 infections reported on each individual's day of assessment was a significant predictor of subjective age. The association between a higher infection rate and a younger subjective age was stronger among individuals who were chronologically older and those who reported stronger health concerns. Our findings thus suggest that individuals-particularly those who are older and those who are more worried about their health-feel younger at times when COVID-19 infection rates are higher, which might be a mechanism to cope with the virus threat. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Impact of Breed on the Fecal Microbiome of Dogs under the Same Dietary Condition.
The gut microbiome influences the health and well-being of dogs. However, little is known about the impact of breed on the fecal microbiome composition in dogs. Therefore, we aimed to investigate the differences in the fecal microbiome in three breeds of dog fed and housed under the same conditions, namely eight Maltese (8.0 ± 0.1 years), eight Miniature Schnauzer (8.0 ± 0.0 years), and nine Poodle dogs (8.0 ± 0.0 years). Fresh fecal samples were collected from the dogs and used to extract metagenomic DNA. The composition of the fecal microbiome was evaluated by 16S rRNA gene amplicon sequencing on the MiSeq platform. A total of 840,501 sequences were obtained from the 25 fecal samples and classified as Firmicutes (32.3-97.3% of the total sequences), Bacteroidetes (0.1-62.6%), Actinobacteria (0.2-14.7%), Fusobacteria (0.0-5.7%), and Proteobacteria (0.0-5.1%). The relative abundance of Firmicutes was significantly lower in the Maltese dog breed than that in the other two breeds, while that of Fusobacteria was significantly higher in the Maltese than in the Miniature Schnauzer breed. At the genus level, the relative abundance of Streptococcus, Fusobacterium, Turicibacter, Succinivibrio, and Anaerobiospirillum differed significantly among the three dog breeds. These genera had no correlation with age, diet, sex, body weight, vaccination history, or parasite protection history. Within a breed, some of these genera had a correlation with at least one blood chemistry value. This study indicates that the composition of the fecal microbiome in dogs is affected by breed.


Trends in divorce and marriage around the world.
"A study of 27 [developed] nations indicated that divorce rates rose in 25 of the nations from 1950 to 1985 while marriage rates declined in 22 of the nations. Nations with higher divorce rates in 1950 had steeper increases in the divorce rate subsequently, supporting a critical-mass hypothesis."


Increased plasma asymmetric dimethylarginine level is associated with ascending aorta dilatation: a case-control study.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. We aimed to determine plasma ADMA levels in patients with ascending aorta dilatation in comparison to those without aorta dilatation, and to evaluate the diagnostic, predictive, and prognostic value of serum ADMA level for aorta dilatation. This was a cross-sectional case-control study. A total of 104 consecutive patients (female/male, 35/69; mean age, 62.75 ± 13.11 years) diagnosed with ascending aorta dilatation (≥ 4.5 cm) on echocardiography (case group), and 52 age-and gender-matched patients (female/male, 17/35; mean age, 63.44 ± 7.56 years) with normal aorta dimensions (≤ 3.8 cm) (control group) were included. Routine biochemical and haematological analysis in addition to measurement of serum ADMA level were performed. The mean diameter of ascending aorta measured on echocardiography was 4.95 ± 0.57 cm and 3.34 ± 0.36 cm in patients with aorta dilatation and those without aorta dilatation, respectively (p < 0.001). Serum ADMA level was significantly higher in patients with aorta dilatation than in the control group (1.70 ± 1.12 μmol/L vs. 0.79 ± 0.76 μmol/L, respectively, p < 0.001). There was significant positive correlation between ADMA level and aortic diameter in Spearman correlation analysis (r = 0.317, p < 0.001). In linear regression analysis, ADMA was found to be a significant independent predictor of aorta diameter (Beta = 0.26, p < 0.001). Receiver-operator characteristic curve analysis also revealed that serum ADMA cut-off level over 0.29 μmol/L predicts aorta dilatation (≥ 4.5 cm) with 94% sensitivity and 92% specificity and with high ac-curacy (area under curve: 0.786; 95% confidence interval: 0.709-0.863, p < 0.001). Serum ADMA level is diagnostic for ascending aorta dilatation with high sensitivity and specificity, and should be considered for use in clinical diagnosis of aorta dilatation.


Dysfunction of erythropoietin-producing interstitial cells in the kidneys of ICR-derived glomerulonephritis (ICGN) mice.
Anemia is a major secondary symptom in chronic renal disorder (CRD), but the precise cause of insufficient production of erythropoietin (EPO) remains unclear owing to the controversial localization of EPO-producing cells in the kidneys. The ICR-derived glomerulonephritis (ICGN) mouse, a new hereditary nephrotic mouse, is an appropriate model of anemia associated with CRD. By using an amplified in situ hybridization technique, we detected and counted the renal EPO-producing cells under both normoxic and hypoxic conditions. The expression levels of renal EPO mRNA were quantified and oxygen gradients were also assessed immunohistochemically. Amplified in situ hybridization clarified that EPO-producing cells were peritubular interstitial cells in the middle region of renal cortex in both ICR and ICGN mice. Hypoxia (7% O2) induced low oxygen tension in proximal tubular epithelial cells of renal cortex, and increased the expression of EPO mRNA and the number of EPO-producing cells in both ICR and ICGN mice. However, hypoxia did not increase the serum EPO levels in ICGN mice. The ICGN mouse is a good model for anemia associated with CRD, and the suppression of EPO protein production in the renal EPO-producing cells is considered to be a potential cause of anemia associated with CRD.


Religion, Spirituality, and Ethics in Psychiatric Practice.
The interface of religion, spirituality, and psychiatric practice has long been of interest to the ethical psychiatrist. Some prominent early psychotherapists had a strained relationship with religion and spirituality. They posited that religion and spirituality were forms of mental illness, which discouraged the discussion of these values during treatment despite the fact that many patients subscribed to a religious or spiritual viewpoint. Contrarily, others supported a harmonious relationship with religion and spirituality and served as trailblazers for the incorporation of religion and spirituality into psychiatric treatment.As the field of psychiatry continues to evolve, additional dimensions of the relationship between religion, spirituality, and psychiatric practice must be explored. Today, many modern psychiatrists appreciate the importance of incorporating religion and spirituality into treatment, but questions such as whether it is ethical to practice psychiatry from a particular religious or spiritual viewpoint or for psychiatrists to advertise that they subscribe to a particular religion or spirituality and to engage in religious or spiritual practices with their patients remain nuanced and complex. In this resource document, the authors put forth and examine the ramifications of a bio-psycho-social-religious/spiritual model for psychological development and functioning, with this fourth dimension shifting the focus from symptom reduction alone to include other aspects of human flourishing such as resilience, meaning-making, and hope.


Asymmetric one-dimensional random walks.
For one-dimensional surface diffusion in the presence of fields, movement of particles has to be considered as a random walk in which jumps to the right occur at a rate different from jumps to the left. Moments of the displacement distribution are worked out for such a one-dimensional walk to nearest-neighbor sites as well as by longer jumps to second nearest neighbors. The actual distribution of displacements, and how it changes as the asymmetry of the jump rates changes, is also examined, as this provides important information about the participating jump processes. We show that deriving the third moment gives a clear indication of the asymmetry in the random walk.


The probability of blindness in patients treated for glaucoma.
To investigate the risk factors and probability of blindness in patients treated for glaucoma. The study design was a retrospective, hospital-based, clinical chart, review study. Medical records were reviewed from patients seen between January 2003 and December 2003 at the Kaohsiung Chang Gung Memorial Hospital eye clinic, who had been diagnosed with glaucoma in 1986 or later and who had been treated for at least 2 years for glaucoma. A total of 186 charts were reviewed, which included 66 patients who were blind in at least one eye from glaucoma on presentation. A total of 172 patients and 290 eyes were followed-up for a mean duration of 10.6 +/- 4.67 years. Twenty seven patients and 31 eyes developed blindness from glaucoma during follow-up. The Kaplan-Meier survival estimate at 16 years was 28.6% for glaucoma-related blindness in at least one eye. A worse visual field on presentation, older age, and poor compliance during therapy were significantly associated with the development of blindness. Glaucoma type, a gender difference, systemic disease, greater intraocular pressure fluctuation in the last year of therapy and blindness in one eye on presentation did not show a significant relationship with the rate of development of blindness. Blindness from treated glaucoma is considerable. Our results gave a 28.6% probability of blindness at 16 years in at least one eye. An older age, poor compliance and a worse visual field on presentation were significant risk factors.


In situ adhesion measurements utilizing layer-by-layer functionalized surfaces.
The adhesion between poly(dimethylsiloxane) (PDMS) hemispheres coated with layer-by-layer (LbL) assemblies of polyelectrolytes and rigid, planar substrates was investigated using Johnson, Kendall, and Roberts (JKR) contact mechanics. Measurements were performed against amine-functionalized glass slides both in air and in aqueous solutions of controlled pH. Despite the increased density of negatively charged carboxylate groups, LbL-functionalized PDMS exhibited lower adhesion because of the combined effects of increased surface roughness and the high Young's modulus of the coating. Measurements of coated PDMS in aqueous solutions revealed tunable adhesion behavior dominated by pH-mediated changes in the mechanical properties of the coating. Smoothing the surface of the LbL coatings by aqueous salt annealing led to a significant increase in adhesion. Our results suggest that LbL assembly can be an effective means of surface functionalization for in situ adhesion measurements, but understanding and predicting the adhesion behavior requires comprehensive knowledge of the chemical, mechanical, and topological properties of the coating and how such properties change in response to the ambient environment.


Folic acid involvement in cyclopropane fatty acid synthesis in lactobacilli.
Henderson, Thomas O. (North Carolina State University, Raleigh), John J. McNeill, and S. B. Tove. Folic acid involvement in cyclopropane fatty acid synthesis in lactobacilli. J. Bacteriol. 90:1283-1287. 1965.-Evidence for the involvement of folic acid in the synthesis of lactobacillic acid (11,12-methyleneoctadecanoic acid) was obtained with Lactobacillus plantarum and L. casei. L. plantarum, in the presence of aminopterin, incorporated 25% less radioactivity from methionine-methyl-C(14) into long-chain fatty acids than did control cultures, whereas the incorporation of acetate-1-C(14), representing overall fatty acid synthesis, was the same in both conditions. Control cultures of L. plantarum contained 3 to 4.5 times more lactobacillic acid than did aminopterin-grown cultures. Similarly, L. casei, in the presence of folic acid, synthesized six times more lactobacillic acid than did folic-deficient cultures. The results of this study indicate that coenzymes of the folic acid group are involved in the synthesis of lactobacillic acid in these organisms.


Post mortem, ultrastructural cardiac muscle changes and anthracycline toxicity.
Anthracycline induced cardiomyopathy is commonly evaluated using the ultrastructural investigation of myocardial tissue. This is based to a large degree on subjectively evaluated, studies of post-mortem material which report various fin structural changes of cardiac tissue as being characteristic of this cardiomyopathy. We have studied the morphological variations of normal myocardial tissue in rats following perfusion fixation and immersion fixation of tissue obtained at death as well as at time points up to 6 hours after death, to examine the fine structural changes associated with immersion fixation and post mortal artefacts. Mitochondria profile area (reflecting mitochondrial swelling--a factor constantly reported as typical of anthracycline damage) increased significantly (p less than 0,01) if there was any delay between cell death and fixation. Many other fine structural changes were noted. We conclude that studies of this nature should ideally be carried out in experimental systems using perfusion fixation. Fixation procedures must always be defined in detail. If post mortem material must be used adequate information on the duration of the autolytic period must be given.


Controlling HIV-1: Non-Coding RNA Gene Therapy Approaches to a Functional Cure.
The current treatment strategy for HIV-1 involves prolonged and intensive combined antiretroviral therapy (cART), which successfully suppresses plasma viremia. It has transformed HIV-1 infection into a chronic disease. However, despite the success of cART, a latent form of HIV-1 infection persists as integrated provirus in resting memory CD4(+) T cells. Virus can reactivate from this reservoir upon cessation of treatment, and hence HIV requires lifelong therapy. The reservoir represents a major barrier to eradication. Understanding molecular mechanisms regulating HIV-1 transcription and latency are crucial to develop alternate treatment strategies, which impact upon the reservoir and provide a path toward a "functional cure" in which there is no detectable viremia in the absence of cART. Numerous reports have suggested ncRNAs are involved in regulating viral transcription and latency. This review will discuss the latest developments in ncRNAs, specifically short interfering (si)RNA and short hairpin (sh)RNA, targeting molecular mechanisms of HIV-1 transcription, which may represent potential future therapeutics. It will also briefly address animal models for testing potential therapeutics and current gene therapy clinical trials.


Basal metabolic rate and body composition in patients with post-polio syndrome.
The aim of this study was to compare basal metabolic rate (BMR) of post-polio syndrome (PPS) patients with healthy individuals and to determine its correlation to body composition. BMR (kcal/day) was determined by indirect calorimetry and body composition by dual energy X-ray absorptiometry. BMR was lower in the PPS patient group than in the control group, although it was similar in both groups when adjusted for body surface area, total body mass (TBM), lean body mass (LBM) and fat-free mass (FFM). PPS patients also showed reduced TBM, LBM and FFM in relation to controls. As muscle energy expenditure while at rest contributes only 20% to the BMR, a proportional reduction in BMR and FFM or LBM could suggest that muscle mass or other factors may interfere more than predicted. It was concluded that the prediction of BMR from the Harris-Benedict equation in PPS patients must be carefully reviewed.


The structure and expression of genes encoding serologically undetected HLA-C locus antigens.
Approximately 20 to 50% individuals in every race are untypable by human alloantisera for at least one allele of HLA-C locus and the surface expression of HLA-C locus Ag in such an individual (HLA-C blank Ag) remains unknown. To investigate the structure and the surface expression of HLA-C blank Ag, two genes (Cb-1 and Cb-2) encoding HLA-C blank Ag were cloned and their primary structures were determined and compared with other HLA-C locus genes. The similarity of amino acids between Cb-1 and Cw1 was the highest among HLA-C locus genes previously published. Five amino acid substitutions between these molecules were shown to be located on the beta-strand of alpha 1 and alpha 2 domains, suggesting that they might change the conformational allodeterminants on the alpha-helical region of Cw1 which were recognized by antibodies. On the other hand, Cb-2 was the closest to Cw2.2. Six of nine amino acid substitutions between these molecules were observed on alpha 1 and alpha 2 domains, whereas three other substitutions were located on the leader peptide, the alpha 3 domain and the transmembrane. Two substitutions (residues 73 and 163) of the alpha-helical region of the alpha 1 and alpha 2 domains and one (residue 16) of exposed loop may make new allodeterminants which are not recognized by anti-Cw2 sera as well as other alloantisera. The surface expression of these genes was examined on transfected mouse L cells and human B cell line. Both gene products were expressed stably on the surface of these cells. These results suggest that HLA-C blank Ag are most probably expressed on cells in HLA-C blank individuals and that the primary structures of these Ag, which were not detectable by the available alloantisera, may be incapable of generating corresponding alloantibodies.


Diagnostic exercise: papulovesicular dermatitis in rhesus macaques (Macaca mulatta).
Eleven rhesus monkeys developed multifocal erythematous and a vesicular rash. Most recovered spontaneously, but a 21-year-old female became moribund and was euthanized. Findings were of vesicular dermatitis and widespread multifocal hemorrhagic necrosis of the lungs and other viscera, with intralesional intranuclear inclusions. Simian varicella virus was identified as the cause by polymerase chain reaction analysis and serologic testing.


Does early wound infection after elective orthopaedic surgery lead on to chronic sepsis?
Infection is an uncommon, but occasionally devastating, complication of orthopaedic surgery. The definition of post-operative infection remains problematic. A high rate of early post-operative sepsis has previously been reported using a clinical definition of wound infection as recommended by the Surgical Infection Study Group. The purposes of this study is to determine the rate of ongoing wound problems and deep sepsis 1 year after these early wound infections. Of 1131 consecutive orthopaedic procedures, there were 70 wound infections occurring within 30 days of surgery. Adequate follow-up data were obtained in 67 (97%) of the 69 patients alive at 1 year. Of these 67, three had definite evidence and two possible evidence of ongoing wound problems and/or deep sepsis. It is concluded that early post-operative wound infection as defined by the Surgical Infection Study Group is a poor predictor (4-10%) of ongoing wound problems and deep sepsis at 1 year. All of the confirmed cases of late sepsis were found to be associated with revision arthroplasty and/or pin tract sepsis.


[Effect of triple-induction regimen including all-trans retinoic acid, arsenic trioxide plus anthracyclines for adults with non-high-risk acute promyelocytic leukemia].
Objective: To analyze the effect of triple-induction regimen including all-trans retinoic acid(ATRA), arsenic trioxide(ATO) plus anthracyclines and double-induction regimen including ATRA and ATO for adults with non-high-risk acute promyelocytic leukemia(APL). Methods: The clinical data of adult patients with non-high-risk APL who were first diagnosed and admitted to the Henan Provincial People's Hospital from January 2009 to December 2019 were retrospectively analyzed. All patients were divided into triple-induction group and double-induction group according to the treatment. The general data of patients, blood routine, coagulation function changes and blood transfusions during the induction period were collected, and the complete remission rate, early mortality and prognosis of two groups were analyzed. Results: A total of 164 patients were enrolled, including 86 males and 78 females, and the M(Q1,Q3) of their age was 41(18, 70) years. Among them, 75 were in triple-induction group and 89 in double-induction group. The white blood cell(WBC) counts of triple-induction group on day 7th and 14th after induction were (9.49±6.10)×109/L and (5.43±3.97)×109/L, while those in double-induction group were (15.17±17.06)×109/L and (13.37±12.59)×109/L, the differences were statistically significant (both P<0.05). In addition, the peak of WBC in the triple-induction group was lower than that in the double-induction group [13.8(6.3,89.7)×109/L vs 19.2(3.8,112.8)×109/L, P=0.019]. On day 7th after induction, the platelet(PLT) counts in the triple-induction group was lower than that in the double-induction group [27(11,147)×109/L vs 45(8, 183)×109/L, P=0.014]. However, the difference was not statistically significant in PLT counts between the two groups on day 14th, 21st and 28th, or in PLT transfusions during induction (all P>0.05). After treatment, it was observed only in a few patients of two groups that the prothrombin time(PT) elongation ≥3 s and/or activated partial thromboplastin time(APTT) elongation ≥10 s, and the difference was not statistically significant (all P>0.05). The incidence of induced differentiation syndrome in the triple-induction group was lower than that in the double-induction group (2.7% vs 12.4%, P=0.022) The early mortality rate was lower than that in the double-induction group (1.3% vs 5.6%), but the difference was not statistically significant (P>0.05). There were no statistically significant differences in the early complete remission rate, genetic remission rate, molecular remission rate, relapse rate, overall survival (OS) rate and disease-free survival (DFS) rate between the two groups. Conclusion: For adults with non-high-risk APL, the triple-induction therapy can reduce the counts and peaks of WBC, and reduce the incidence of induced differentiation syndrome.


Ischemia and reperfusion reduce the endogenous basic fibroblast growth factor in rat skeletal muscles: an immunohistochemical study.
Polyclonal antibodies directed against human recombinant basic fibroblast growth factor were used in immunohistochemical studies to localize this growth factor in normal and wounded rat skeletal muscles. According to the intensity of the stain, three main classes of fibers could be identified: the strongly, moderately, and weakly stained fibers. Basic fibroblast growth factor immunoreactivity was found mainly in the extracellular matrix, primarily in the endomysium, which includes the heparin-containing basal lamina, and also in the capillary basal membrane of both normal and wounded muscles; however, the signal intensity was much stronger in normal muscles. The distribution of basic fibroblast growth factor in wounded muscles became markedly heterogeneous and sparse. After 4 hours of ischemia, about 40% of skeletal muscle fibers lost their basic fibroblast growth factor immuno-reactivity. Muscles which underwent 4 hours of ischemia and 24 hours of reperfusion had only a diminished basic fibroblast growth factor immunoreactivity. The pathologic results supported the concept of destroyed cell connection and fiber necrosis in ischemic and reperfused muscles. Potential mechanisms involved in this reduced concentration of basic fibroblast growth factor in wounded muscles may include oxygen free radical activation, a generalized effect of the inflammatory response, and reduced secretion of endogenous basic fibroblast growth factor. These results are only partially compatible with the established mitogenic role of this growth factor and suggest that a reduction of endogenous fibroblast growth factor may partly contribute to a delay in wound healing.


Adsorption characteristics of chloramphenicol onto powdered activated carbon and its desorption performance by ultrasound.
In this work, the adsorption characteristics, including adsorption kinetic, isotherm and thermodynamics of chloramphenicol (CAP) onto powdered activated carbon (PAC), were carried out, and the feasibility of using ultrasound to regenerate saturated PAC in aqueous solution was evaluated. The adsorption results demonstrated that the adsorption mechanism was a complex process including surface adsorption, external liquid membrane diffusion and intraparticle diffusion as well, and the adsorption process was endothermic and non-spontaneous. The optimal conditions for PAC regeneration were as follows: acoustic density of 0.36 W/mL, saturated carbon dosage of 1.0 g/L and pH value of 10.36. The analysis of thermogravimetric analysis (TGA), Fourier transform infrared spectrometry (FTIR), Brunauer-Emmett-Teller (BET) surface area, pore size distribution and scanning electron microscopy (SEM) of PAC samples revealed that ultrasound mainly acted on surface functionalities, meso-pores and macro-pores of PAC through hydroxyl radical oxidization, high-pressure shock waves and high-speed microjets due to cavitation effect. This study highlighted that ultrasound could be efficiently desorbing CAP from saturated PAC. Practical applications of this method for PAC regeneration with complex natural matrices under environmentally realistic conditions were conducted and the adsorption capacity of the regenerated PAC decreased.


Clinical applications of the Process Model of Family Functioning.
This paper discusses clinical applications of the Process Model of Family Functioning. It provides a framework for conducting and systematically recording a family assessment, and can help clinicians achieve and use improved control of clinical sessions to increase their diagnostic and therapeutic effectiveness. Ways of using FAM-III, a self-report test derived from the model, to confirm or amplify a clinical assessment and to assist or monitor therapeutic interventions are discussed. Viewing psychological and family systems theories as complementary, the model provides a rationale for integrating both sets of theories to achieve a more pluralistic view of pathogenesis and a more selective choice of therapies. An extended example illustrates the concurrent use of individual and family therapies. Other topics discussed include the role of family strengths, the derivation of therapeutic goals, moving from content to perceive underlying structure and process, making the conceptual shift from group-of-two to conceptualizing the family as a group (system) in equilibrium.


Multispecies Occupations Involving Equines: An Action-Oriented Inquiry to Inform Occupational Therapy Practitioners.
Research related to human-animal engagement often fails to address the complexity and nuance present in occupations and occupational therapy services that incorporate animals. The goal of this research was to develop a basic understanding of multispecies occupations (MSO) involving humans and equines, focusing on the action-oriented processes and transactions during socialization in outdoor, non-therapeutic contexts. We employed a multi-modal qualitative design with interviews and videography with n = 6 horse-human dyads, creating opportunities to understand and represent engagement beyond anthropocentric norms. Findings included a variety of dyad-specific features of occupation, including processes of embodied communication, the presence of behavioral synchrony, and perceptions of attunement arising from these processes. Examining MSO via a multi-modal inquiry offers new perspectives about the nature and experience of such occupations and supports a deeper understanding of potential mechanisms of change when animals are incorporated in occupational therapy interventions and practice.


[Mechanism of emetic action of adrenaline and histamine in the dog].
It has been established in dog experiments that phentolamine prevents the emetic action of adrenaline whereas diphenhydramine the emetic effect of histamine. Both the drugs in the doses studied do not produce any effect on vomiting induced by L-DOPA. The dopamine blockers, etaperazine, haloperidol and metoclopramide given in the doses suppressing the emetic action of L-DOPA do not prevent the adrenaline- and histamine-induced vomiting. It is assumed that the emetic action of adrenaline is effected in dogs via alpha-adrenoreceptors, whereas the histamine-induced vomiting via H1-histamine receptors of the trigger zone of the vomiting center.


The Role of Post-Translational Modifications on Prion-Like Aggregation and Liquid-Phase Separation of FUS.
Subcellular mislocalization and aggregation of the human FUS protein occurs in neurons of patients with subtypes of amyotrophic lateral sclerosis and frontotemporal dementia. FUS is one of several RNA-binding proteins that can functionally self-associate into distinct liquid-phase droplet structures. It is postulated that aberrant interactions within the dense phase-separated state can potentiate FUS's transition into solid prion-like aggregates that cause disease. FUS is post-translationally modified at numerous positions, which affect both its localization and aggregation propensity. These modifications may influence FUS-linked pathology and serve as therapeutic targets.


Factors associated with the perceived benefits and barriers to physical activity in liver cirrhosis.
To analyze the sociodemographic and clinical factors associated with the perceived benefits and barriers to physical activity (PA) in subjects with liver cirrhosis. This cross-sectional study assessed 102 outpatients with liver cirrhosis regarding the clinical and sociodemographic profile and the perceived benefits and barriers to PA by the Exercise Benefits and Barriers Scale and muscle strength. A Generalized Step-Forward linear regression analysis was used to identify the factors associated. The participants were 59±10 years and 60.8% were men. Around 29.4% had ascites decompensation. Perceived benefits and barriers were associated with the presence of ascites (95%CI -0.079 - 0.03; p=0.06 and 95%CI 0.003 - 0.217; p=0.045, respectively). In the group with ascites, both benefits and barriers were associated with muscle strength. In the group without ascites, benefits were associated with cardiovascular risks and no association was observed with barriers to physical activity. Perceived benefits and barriers to physical activity are associated with intrinsic factors such as the presence of ascites and cardiovascular risk in individuals with liver cirrhosis. The results of this study highlight key elements that must be considered for increasing physical activity in this population.


Effect of oral glucose on the rate of metabolism of ethanol in humans.
We have tested whether the effect of carbohydrate on the rate of alcohol metabolism can be reproduced by glucose alone. Ten male subjects were given ethanol by intravenous infusion until a steady state was established and 100 g glucose in solution was then taken orally. The rate of alcohol metabolism, measured as the rate of infusion required to maintain a constant breath alcohol reading, increased significantly after glucose but there were differences between the subjects. The presence or absence of a change in the rate of alcohol metabolism after glucose was associated with the subject's fasting rate and with their glucose tolerance.


Natural tooth pontic fixed partial denture using resin composite-reinforced glass fibers.
This article describes the rationale and method of using glass fibers reinforced with resin composite as an external framework to reuse a patient's own natural anterior tooth as a pontic, after extraction.


Novel spectroscopic technique for in situ monitoring of collagen fibril alignment in gels.
Development of collagen fibril alignment in contracting fibroblast-populated and externally tensioned acellular collagen gels was studied using elastic scattering spectroscopy. Spectra of the backscattered light (320-860 nm) were acquired with a 2.75-mm source-detector separation probe placed perpendicular to the gel surface and rotated to achieve different angles to the collagen fibril alignment. Backscatter was isotropic for noncontracted/unloaded gels (disorganized matrix). As gels were contracted/externally loaded (collagen alignment developed), anisotropy of backscatter increased: more backscatter was detected perpendicular than parallel to the direction of the fibril alignment. An "anisotropy factor" (AF) was calculated to characterize this effect as the ratio of backscatter intensities at orthogonal positions. Before contraction (or zero strain) the AF was close to unity at all wavelengths. In contrast, at 72 h, backscatter anisotropy varied from AF(400 nm) = 2.14 +/- 0.29 to AF(700 nm) = 3.04 +/- 0.48. It also increased over threefold up to a strain of 20%. The AF strongly correlated with the contraction time/strain. Different directions of the backscatter were detected in gel zones with known differences in the matrix alignment. Thus, backscatter anisotropy allows in situ nondestructive determination of collagen fibril alignment and quantitative monitoring of its development.


Eye-hand coordination in essential tremor.
Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients and 14 controls performed saccades with and without simultaneous pointing movements to the same targets, and with and without a gap between the disappearance of the fixation point and the appearance of the target. Eye movements were recorded with the magnetic search-coil method, hand movements with an ultrasound-emitting probe. ET patients did not have saccadic dysmetria, and contrary to normal subjects their saccadic latency did not decrease during combined eye-hand movements compared with saccades performed in isolation. Hand movements had a longer duration in ET patients, with decreased peak acceleration, an increased latency of the peak velocity, and peak deceleration. In conclusion, this first study on eye-hand coordination in ET revealed abnormal kinematic changes in the early phase of pointing movements. These changes might be related to cerebellar disease but they are independent of the intention tremor component and saccade performance.


Rhodium-Catalyzed Transnitrilation of Aryl Boronic Acids with Dimethylmalononitrile.
An efficient transnitrilation of aryl boronic acids with dimethylmalononitrile (DMMN) is described. This rhodium-catalyzed electrophilic cyanation presents a novel approach to prepare aryl nitriles by using a carbon-bound cyanating reagent which undergoes cross-coupling with the aryl boronic acid. The reaction expands the degree of functional-group compatibility exhibited by the transnitrilation of aryl Grignard and aryllithium reagents. A variety of aryl boronic acid derivatives and dialkylmalononitriles were amenable to the transnitrilation.


Neonatal small left colon syndrome: report of two cases.
Two cases of neonatal small left colon syndrome are described. This syndrome usually is seen as bowel obstruction in the neonate with characteristic roentgenographic features resembling those of Hirschsprung's disease. In view of the usual improvement after contrast enema, a trial of conservative management seems warranted. Rectal biopsy may be the only way to differentiate those patients who do not improve from those with Hirschsprung's disease.