Peroxiredoxin-6 protects against mitochondrial dysfunction and liver injury during ischemia-reperfusion in mice.
Hepatic ischemia-reperfusion (I/R) injury is an important complication of liver surgery and transplantation. Mitochondrial function is central to this injury. To examine alterations in mitochondrial function during I/R, we assessed the mitochondrial proteome in C57Bl/6 mice. Proteomic analysis of liver mitochondria revealed 234 proteins with significantly altered expression after I/R. From these, 13 proteins with the greatest expression differences were identified. One of these proteins, peroxiredoxin-6 (Prdx6), has never before been described in mitochondria. In hepatocytes from sham-operated mice, Prdx6 expression was found exclusively in the cytoplasm. After ischemia or I/R, Prdx6 expression disappeared from the cytoplasm and appeared in the mitochondria, suggesting mitochondrial trafficking. To explore the functional role of Prdx6 in hepatic I/R injury, wild-type and Prdx6-knockout mice were subjected to I/R injury. Prdx6-knockout mice had significantly more hepatocellular injury compared with wild-type mice. Interestingly, the increased injury in Prdx6-knockout mice occurred despite reduced inflammation and was associated with increased mitochondrial generation of H(2)O(2) and dysfunction. The mitochondrial dysfunction appeared to be related to complex I of the electron transport chain. These data suggest that hepatocyte Prdx6 traffics to the mitochondria during I/R to limit mitochondrial dysfunction as a protective mechanism against hepatocellular injury.


Effect of haemodynamic changes during rapid atrial pacing on determination of sinus node recovery time.
Arterial blood pressure was continuously monitored during rapid atrial pacing in 31 patients with different types of heart disease to determine sinus node recovery time and corrected sinus node recovery time. Pacing was initiated at 70 beats/min and increased stepwise to 160 beats/min. One to one atrioventricular conduction was maintained throughout the one minute stimulation period. Blood pressure fell initially during at least one stimulation period in 21 of our patients and at pacing rates up to 130 beats/min in 18. Once blood pressure had fallen during overdrive pacing maximal sinus node recovery time and maximal corrected sinus node recovery time could not be prolonged by increasing the pacing rate. Sinus node recovery time and corrected sinus node recovery time during the pacing induced fall in blood pressure was significantly shorter than those during stimulation runs with constant blood pressure. No pacing induced fall in blood pressure and no relation between changes in blood pressure and sinus node recovery time were evident in 10 of the 31 patients. Sinus node recovery time is therefore influenced by alterations in autonomic tone due to pacing induced haemodynamic changes.


Fatigue in chronic liver disease patients: prevalence, pathophysiology, and management.
Fatigue is the most commonly encountered symptom in patients with chronic liver disease (CLD). The resulting decrease in quality of life contributes markedly to the societal costs of fatigue. Moreover, fatigue is associated with social dysfunction, increased daytime somnolence, impaired working ability, and increased risk of mortality. Fatigue is not related to the severity of the underlying liver fibrosis or dysfunction. In CLD patients, fatigue manifests with both central symptoms, characterised by cognitive impairment, sleep disturbance, apathy, and autonomic dysfunction, and peripheral symptoms, characterised by decreased exercise tolerance and reduced physical activity levels. The pathogenesis of fatigue in CLD is multifactorial and involves changes in the brain-liver axis resulting from changes in inflammatory cytokines or the gut microbiome. Numerous interventions have attempted to alleviate fatigue in CLD by improving its central and peripheral manifestations or the underlying liver disease. Currently, however, there are no widely accepted or effective treatments for fatigue in CLD patients. In this review, we highlight the problem of fatigue in CLD, the current theories regarding its pathogenesis, and current approaches to its treatment.


Discovery of novel potent PI3K/mTOR dual-target inhibitors based on scaffold hopping: Design, synthesis, and antiproliferative activity.
The PI3K/AKT/mTOR pathway is one of the most common dysregulated signaling cascade responses in human cancers, playing a crucial role in cell proliferation and angiogenesis. Therefore, the development of anticancer drugs targeting the PI3K and mTOR pathways has become a research hotspot in cancer treatment. In this study, the PI3K selective inhibitor GDC-0941 was selected as a lead compound, and 28 thiophenyl-triazine derivatives with aromatic urea structures were synthesized based on scaffold hopping, serving as a novel class of PI3K/mTOR dual inhibitors. The most promising compound Y-2 was obtained through antiproliferative activity evaluation, kinase inhibition, and toxicity assays. The results showed that Y-2 demonstrated potential inhibitory effects on both PI3K kinase and mTOR kinase, with IC50 values of 171.4 and 10.2 nM, respectively. The inhibitory effect of Y-2 on mTOR kinase was 52 times greater than that of the positive drug GDC-0941. Subsequently, the antitumor activity of Y-2 was verified through pharmacological experiments such as AO staining, cell apoptosis, scratch assays, and cell colony formation. The antitumor mechanism of Y-2 was further investigated through JC-1 experiments, real-time quantitative PCR, and Western blot analysis. Based on the above experiments, Y-2 can be identified as a potent PI3K/mTOR dual inhibitor for cancer treatment.


Physiologic isolation of the canine proximal fibular epiphysis on a vascular pedicle.
In order to create a model for epiphyseal growth plate transplantation by microvascular technique, a well-defined donor site was established. Dissection of latex-injected adult and juvenile dogs established the vascular supply to the proximal canine fibula. By isolating 7 cm of proximal fibula on the popliteal vessels, the nutrient supply to the epiphyses, metaphysis, and diaphysis is retained. This preserves the nutrient arterial supply to the fibula originating from the cranial tibial artery, the caudal tibial artery, and the small blood vessels from these to the epiphysis. Perfusion of the graft through the defined vascular pedicle was confirmed using 141Ce-labeled microspheres. These results showed a perfusion of the established graft that was as great as or greater than the control, unoperated side. It is concluded that the technique described for isolation can be used for developing a model for vascularized transplantation of epiphyseal growth cartilage in canines.


Dose titration of steroidal and non-steroidal topical anti-inflammatory agents.
Although there is a variety of animal models available, neither a single assay system nor the results of the various assays permit absolute protection of relative anti-inflammatory potency. Equally, current clinical dose titration studies, although more reliable, provide only gross estimates of therapeutic potency when conducted in certain clinical situations in a double-blind randomized fashion. This paper delineated clinical means to titrate more objectively and accurately therapeutic potency in the patient. Moreover, it has submitted considerations as to how to assess therapeutic anti-inflammatory activity in the complex multi-component process of inflammation accompanying most dermatologic diseases that eventually may permit titration of specific anti-inflammatory compounds on certain tissue components of the inflammatory process.


Lipid-dependent pore formation by antimicrobial peptides arenicin-2 and melittin demonstrated by their proton transfer activity.
This work presents a comparative study of proton transfer activity (PTA) of two cationic (+6) antimicrobial peptides, β-structural arenicin-2 and α-helical melittin. A new approach was proposed for the detection of passive proton transfer by using proteoliposomes containing bacteriorhodopsin, which creates a small light-induced electrochemical proton gradient ∆ΔpH. Addition of several nanomoles of the peptides lowers ∆ΔpH that is proximately indicative of the pore formation. The quantitative analysis of sigmoidal dependences of ∆pH on the peptides concentration was carried out using liposomes prepared from PC, PC/PE, PC/PE/PI and PC/PG. Substitution of PC-containing liposomes with PE-containing ones, having negative spontaneous curvature, reduced the PTA of α-helical melittin and increased that of β-structural arenicin-2. This result indicates an essential difference in the pore formation by these peptides. Further increase of PTA in response to arenicin-2 (in contrast to melittin) was observed in the liposomes prepared from PC/PE/PI. The data analysis leads to the conclusion that PTA is influenced by (i) efficiency of the pore assemblage, which depends on the structure of pore-forming peptides, and the spontaneous curvature of lipids and (ii) the presence of mobile protons in the polar head groups of phospholipids.


Modular Design of Biodegradable Ionizable Lipids for Improved mRNA Delivery and Precise Cancer Metastasis Delineation In Vivo.
Lipid nanoparticles (LNPs) represent the most clinically advanced nonviral mRNA delivery vehicles; however, the full potential of the LNP platform is greatly hampered by inadequate endosomal escape capability. Herein, we rationally introduce a disulfide bond-bridged ester linker to modularly synthesize a library of 96 linker-degradable ionizable lipids (LDILs) for improved mRNA delivery in vivo. The top-performing LDILs are composed of one 4A3 amino headgroup, four disulfide bond-bridged linkers, and four 10-carbon tail chains, whose unique GSH-responsive cone-shaped architectures endow optimized 4A3-SCC-10 and 4A3-SCC-PH lipids with superior endosomal escape and rapid mRNA release abilities, outperforming their parent lipids 4A3-SC-10/PH without a disulfide bond and control lipids 4A3-SSC-10/PH with a disulfide bond in the tail. Notably, compared to DLin-MC3-DMA via systematic administration, 4A3-SCC-10- and 4A3-SCC-PH-formulated LNPs significantly improved mRNA delivery in livers by 87-fold and 176-fold, respectively. Moreover, 4A3-SCC-PH LNPs enabled the highly efficient gene editing of 99% hepatocytes at a low Cre mRNA dose in tdTomato mice following intravenous administration. Meanwhile, 4A3-SCC-PH LNPs were able to selectively deliver firefly luciferase mRNA and facilitate luciferase expression in tumor cells after intraperitoneal injection, further improving cancer metastasis delineation and surgery via bioluminescence imaging. We envision that the chemistry adopted here can be further extended to develop new biodegradable ionizable lipids for broad applications such as gene editing and cancer immunotherapy.


Circulating intercellular adhesion molecule-1 (cICAM-1) concentration in liver disease. Relationship with cholestasis and functioning hepatic mass.
The authors measured immunoenzymatically circulating intercellular adhesion molecule-1 (cICAM-1) concentration in 135 patients with liver disease of either viral or toxic etiology: 13 had acute hepatitis; 58 had mild chronic liver disease; and 64 had cirrhosis (superimposed in 30 by hepatocellular carcinoma). Forty patients with extrahepatic diseases (19 with malignancies) and 28 healthy blood donors were tested as controls. One-way analysis of variance demonstrated a significant variability of cICAM-1 concentration among groups (F = 76.67, P < .0001), the highest value being recorded in acute hepatitis (Bonferroni's test for pairwise comparisons, P < .01). Total bilirubin showed a strong correlation with cICAM-1 (R = 0.766, P < .001). By stepwise multiple regression analysis the independent predictors of cICAM-1 concentration were chosen in the following order: total bilirubin; aspartate aminotransferase; cholinesterase; alpha-1-antitrypsin; and immunoglobulins. Thus, in addition to inflammation, cholestasis and decline of functioning hepatic mass may influence cICAM-1 concentration.


A case of Purtscher retinopathy associated with stent-assisted coil embolization of a middle cerebral artery aneurysm.
This article reports a case of Purtscher retinopathy following therapeutic coil embolization of a middle cerebral artery (MCA) aneurysm. METHODS. Case report. A 53-year-old woman with a history of stent-assisted coil embolization in her left MCA unruptured aneurysm presented with a visual disturbance about 3 hours after the procedure. Her left eye vision was 20/40. Fundus examination of the left eye showed an intraretinal hemorrhage and multiple whitish retinal lesions. The spectral-domain optical coherence tomography (OCT) examination showed focal thickness around the whitish lesions and a hemorrhage site. Three weeks later, the retinal whitish lesions decreased but new multiple intraretinal hemorrhages were found near the previous whitish lesions. Fluorescein angiography revealed the obstruction of an arteriole at the posterior pole. After 5 weeks, all lesions in the fundus photography and OCT were almost gone and her left visual acuity was 20/20. A thorough understanding of clinical findings and mechanism of this disorder, including the possibility of direct emboli during coil embolization rather than secondary emboli from the postoperative coil-thrombus complex formed in the aneurysm after the procedure, is therefore necessary to prevent unwanted ocular complications after coil embolization.


Multifocal disseminated lipoatrophy secondary to intravenous corticosteroid administration in a patient with adrenal insufficiency.
Multifocal disseminated lesions of circumscribed lipoatrophy have not been described as an adverse reaction of intravenously applied drugs. A unique patient with adrenal insufficiency is reported who received corticosteroids intravenously and then had multiple lesions develop that were similar to focal lipoatrophy as known to occur secondary to faulty intradermal injections of corticosteroids.


In vitro assay of erythropoietin: simple determination in a small amount of human serum samples.
An in vitro method for the determination of erythropoietin (EPO) titres in human serum samples was developed to detect low levels of EPO titres in various haematological states. Fetal mouse liver cells (FMLC) were incubated in methylcellulose-containing media, and radioiron incorporation into haem was estimated in cultured FMLC. We could determine the concentrations of EPO from around 20 to 600 mU per ml of a very small amount of serum samples from patients and normal adults. Using this method, EPO titres of normal adults (54 +/- 31 mU/ml), chronic renal failure patients (29 +/- 23 mU/ml), aplastic anaemia patients (545 +/- 74 mU/ml), and polycythaemia vera patients (16 +/- 7 mU/ml) were determined.


The importance of encoding-related neural dynamics in the prediction of inter-individual differences in verbal working memory performance.
Studies of brain-behaviour interactions in the field of working memory (WM) have associated WM success with activation of a fronto-parietal network during the maintenance stage, and this mainly for visuo-spatial WM. Using an inter-individual differences approach, we demonstrate here the equal importance of neural dynamics during the encoding stage, and this in the context of verbal WM tasks which are characterized by encoding phases of long duration and sustained attentional demands. Participants encoded and maintained 5-word lists, half of them containing an unexpected word intended to disturb WM encoding and associated task-related attention processes. We observed that inter-individual differences in WM performance for lists containing disturbing stimuli were related to activation levels in a region previously associated with task-related attentional processing, the left intraparietal sulcus (IPS), and this during stimulus encoding but not maintenance; functional connectivity strength between the left IPS and lateral prefrontal cortex (PFC) further predicted WM performance. This study highlights the critical role, during WM encoding, of neural substrates involved in task-related attentional processes for predicting inter-individual differences in verbal WM performance, and, more generally, provides support for attention-based models of WM.


Effects of response-related music stimulation versus general music stimulation on positive participation of patients with Alzheimer's disease.
Assessing the effects of response-related music stimulation versus general (response-unrelated) music stimulation on positive participation of 11 new patients with Alzheimer's disease. The patients were functioning in the severe and low-moderate ranges of the disease. Positive participation included behaviors such as, singing or rhythmic movements and smiles. Both music conditions relied on the display of music/song videos on a computer screen. In the response-related (active) condition, the patients used a simple hand response and a microswitch to determine music stimulation inputs. In the general (unrelated/passive) condition, music stimulation was automatically presented throughout the sessions. Data showed that six of the 11 patients had higher levels of positive participation in the response-related stimulation condition. The remaining five patients did not have differences between the two conditions. Based on this evidence and previous findings, one might consider the use of the active condition beneficial for daily programs.


Effect of acidic beverages on surface roughness and color stability of artificial teeth and acrylic resin.
The aim was to evaluate the effect of four acidic beverages on the roughness (Ra) and color change (ΔEab) of two brands of artificial teeth and a heat-polymerized acrylic resin (HPAR) for use in a prosthetic base. All materials were divided into 5 groups, according to the used acidic beverage (artificial saliva - control, red wine, orange juice, coke-based, and lemon juice-based soft drink). The immersion process was divided into two stages: T1 - immersion in the acidic solutions for 10 minutes for 14 days; T2 - after T1, the samples were immersed in grape juice for 14 days. The Ra of the samples was evaluated in a rugosimeter and the ΔEab in a spectrophotometer, before and after the immersions. The analysis of variance of one (ΔEab) and two factors (Ra) and Tukey were performed (α=.05). There was a statistical difference for roughness after immersion (T1) for Trilux and Tritone teeth, regardless of the acid solution. For Trilux teeth, all acid solutions increased Ra (P<.05). For Tritone teeth, only the coke-based soft drink did not statistically change Ra. Grape juice (T2) altered Ra only of artificial teeth (P<.05). The color was changed for all materials, after T1 and T2. In general, the acidic solutions changed the Ra and ΔEab of HPAR and artificial teeth after T1. The grape juice altered the roughness only of the artificial teeth, promoting a clinically acceptable color change in the materials.


[Relation between the level of serum CA19-9 and glucose control in inpatients with diabetes].
To investigate the effect of hemoglobin A1c (HbA1c) and glycated albumin (GA) on serum CA199 in diabetic patients. 29 NGT matched control subjects and 371 hospitalized diabetic patients were enrolled. Diabetic patients were divided into satisfactory group (< 6.5%), general group (6.5%-7.5%) and dissatisfactory group (> 7.5%) by the level of HbA1c. The levels of serum CA199 among three groups were compared. The relationship between HbA1c and CA199, GA and CA199 was analysed. Multiple stepwise regression analysis was performed to compare the effect of different variables on CA199 as the independent variables were sex, age, duration, TC, TG, HDL, LDL, FBG, PBG, HbA1c and GA. (1) CA199 level of the group of HbA1c above 7.5% was significantly higher than the group of HbA1c between 6.5% and 7.5% and the group of HbA1c less than 6.5%. (2) The coefficient of correlation between HbA1c and CA199 was 0.394 (P = 0.000), and that was 0.381 between GA and CA199 (P = 0.000). (3) Multiple stepwise regression analysis show standard regression coefficient of HbA1c is 0.364 (P = 0.000). (1) CA199 level of diabetic patient in poor glucose control was significantly higher than the patient in good control. (2) CA199 was positively correlated with FBG, PBG, HbA1c and GA. (3) HbA1c is the independent risk factor of CA199. The elevated CA199 in diabetic patient has close relationship with poor glucose control in a long period.


Challenges for Porcine Reproductive and Respiratory Syndrome (PRRS) Vaccine Design: Reviewing Virus Glycoprotein Interactions with CD163 and Targets of Virus Neutralization.
One of the main participants associated with the onset and maintenance of the porcine respiratory disease complex (PRDC) syndrome is porcine reproductive and respiratory syndrome virus (PRRSV), an RNA virus that has plagued the swine industry for 30 years. The development of effective PRRS vaccines, which deviate from live virus designs, would be an important step towards the control of PRRS. Potential vaccine antigens are found in the five surface proteins of the virus, which form covalent and multiple noncovalent interactions and possess hypervariable epitopes. Consequences of this complex surface structure include antigenic variability and escape from immunity, thus presenting challenges in the development of new vaccines capable of generating broadly sterilizing immunity. One potential vaccine target is the induction of antibody that disrupts the interaction between the macrophage CD163 receptor and the GP2, GP3, and GP4 heterotrimer that protrudes from the surface of the virion. Studies to understand this interaction by mapping mutations that appear following the escape of virus from neutralizing antibody identify the ectodomain regions of GP5 and M as important immune sites. As a target for antibody, GP5 possesses a conserved epitope flanked by N-glycosylation sites and hypervariable regions, a pattern of conserved epitopes shared by other viruses. Resolving this apparent conundrum is needed to advance PRRS vaccine development.


Detection and characterization of B cell epitopes on beta2-glycoprotein I.
Autoantibodies in antiphospholipid syndrome react predominantly with the plasma protein beta2-glycoprotein I (beta2GPI). Work by a large number of investigators has led to considerable progress in detecting and understanding beta2GPI reactivity with autoantibodies. Characterization of B cell epitopes on beta2GPI has benefited from an appreciation of its interactions with anionic phospholipids and a variety of microplate surfaces. In particular, autoantibodies to beta2GPI are of sufficiently low affinity to require high concentrations of antigen for detectable reactivity. Moreover, some microplate surfaces do not support the proper orientation of beta2GPI to allow display of epitopes in a manner accessible to autoantibodies. These concepts have helped to explain previous notions that exposure of cryptic beta2GPI epitopes may require interactions with anionic surfaces. Finally, we review evidence identifying a dominant B cell epitope that is partially defined by residues Gly40 and Arg43 on the amino terminal domain of beta2GPI.


Induction of Defense-Related Physiological and Antioxidant Enzyme Response against Powdery Mildew Disease in Okra (Abelmoschus esculentus L.) Plant by Using Chitosan and Potassium Salts.
Foliar sprays of three plant resistance inducers, including chitosan (CH), potassium sorbate (PS) (C6H7kO2), and potassium bicarbonates (PB) (KHCO3), were used for resistance inducing against Erysiphe cichoracearum DC (powdery mildew) infecting okra plants. Experiments under green house and field conditions showed that, the powdery mildew disease severity was significantly reduced with all tested treatments of CH, PS, and PB in comparison with untreated control. CH at 0.5% and 0.75% (w/v) plus PS at 1.0% and 2.0% and/or PB at 2.0% or 3.0% recorded as the most effective treatments. Moreover, the highest values of vegetative studies and yield were observed with such treatments. CH and potassium salts treatments reflected many compounds of defense singles which leading to the activation power defense system in okra plant. The highest records of reduction in powdery mildew were accompanied with increasing in total phenolic, protein content and increased the activity of polyphenol oxidase, peroxidase, chitinase, and β-1,3-glucanase in okra plants. Meanwhile, single treatments of CH, PS, and PB at high concentration (0.75%, 2.0%, and/or 3.0%) caused considerable effects. Therefore, application of CH and potassium salts as natural and chemical inducers by foliar methods can be used to control of powdery mildew disease at early stages of growth and led to a maximum fruit yield in okra plants.


Thermodynamic profiles for alcohol dehydrogenase action in free solution.
Stopped-flow equipment was used to study the kinetics of the reaction between nicotinamide adenine dinucleotide (NAD) and ethanol, catalyzed by yeast alcohol dehydrogenase. By measuring rates over a range of concentrations of NAD and ethanol and of temperatures, thermodynamic profiles were obtained for the reaction, which occurs by an ordered ternary complex mechanism with NAD adding first. There are significant negative entropies of activation and negative entropy changes for the addition of NAD and of ethanol; the breakdown of the ternary complex is, however, accompanied by a positive entropy of activation. The results are consistent with structural constraints associated with the binding of the substrates, these restraints being to some extent removed when the ternary complex undergoes reaction. The system follows a similar pattern to that found with three different varieties of lactate dehydrogenase.


Long-term prognosis of Salter-Harris type 2 injuries of the distal femoral physis.
The objective of this study was to assess long-term sequelae of Salter-Harris type 2 injuries on growth of the distal femoral physis. A retrospective study of 20 patients with Salter-Harris type 2 distal femoral injuries, who were managed between 1994 and 2003, was carried out. The average period of follow-up was 4 years and 2 months. Mean age of fracture was 11 years (range 8-15 years). We classified radiologically these fractures into three types according to initial displacement on anteroposterior and lateral radiographs (type 1=less than 2 mm; type 2=more than 2 mm, contact between fragments; type 3=no contact). Further subdivision into A and B was made according to the absence or presence of metaphyseal comminution. Clinical and radiological outcomes were evaluated at latest follow-up. Two patients with type 1 injuries were treated conservatively, with no complication. All type 2 and 3 fractures (18) were reduced under general anesthesia. At latest follow-up, 14 patients (70%) sustained a complication due to either epiphysiodesis (12), femoral over-lengthening (1) or associated loss of knee motion (5). Seven out of the 12 epiphysiodeses were initial type B injuries. All type 3 fractures ended with complications. The prognosis of these fractures, often caused by a high-energy trauma, can be severe. Additional subdivision of Salter-Harris type 2 distal femoral physeal injuries is proposed to warn the clinician on specific fracture patterns with higher complication risk. Greater awareness of the numerous growth problems that may occur is needed in type 2B, in which the germinal layer of the physeal cells is damaged.


Individual Efficacy and Community Impact of Ivermectin, Diethylcarbamazine, and Albendazole Mass Drug Administration for Lymphatic Filariasis Control in Fiji: A Cluster Randomized Trial.
Bancroftian filariasis remains endemic in Fiji despite >10 years of mass drug administration (MDA) using diethylcarbamazine and albendazole (DA). The addition of ivermectin to this combination (IDA) has improved efficacy of microfilarial clearance at 12 months in individually randomized trials in nocturnal transmission settings, but impact in a setting of diurnally subperiodic filarial transmission has not been evaluated. This cluster randomized study compared the individual efficacy and community impact of IDA vs DA as MDA for lymphatic filariasis in 35 villages on 2 islands of Fiji. Participants were tested at enrollment for circulating filarial antigen and, if positive, for microfilariae. Weight-dosed treatment was offered according to village randomization. Communities were visited at 12 months and retested for lymphatic filariasis. Infected individuals from Rotuma were retested at 24 months. A total of 3816 participants were enrolled and 3616 were treated. At 12 months, microfilariae clearance was achieved in 72 of 111 participants detected with infection at baseline, with no difference in efficacy between treatment groups: DA, 69.2% (95% confidence interval [CI], 57.2%-79.1%) vs IDA, 62.5% (95% CI, 43.6%-78.2%); risk difference, 11.3 % (95% CI, -10% to 32.7%); P = .30. There was no difference between treatment groups in community prevalence of microfilariae at 12 months or individual clearance at 24 months. We found no difference between IDA and DA in individual clearance or community prevalence of lymphatic filariasis at 12 months, and no improved efficacy following a second annual round of IDA. Possible explanations for the apparent lack of benefit of IDA compared to DA include drug and parasite factors affecting clearance, and higher than expected reinfection rates. Clinical Trials Registration: NCT03177993 and Australian New Zealand Clinical Trial Registry: N12617000738325.


Activation, internalization, and recycling of the serotonin 2A receptor by dopamine.
Serotonergic and dopaminergic systems, and their functional interactions, have been implicated in the pathophysiology of various CNS disorders. Here, we use recombinant serotonin (5-HT) 2A (5-HT2A) receptors to further investigate direct interactions between dopamine and 5-HT receptors. Previous studies in Xenopus oocytes showed that dopamine, although not the cognate ligand for the 5-HT2A receptor, acts as a partial-efficacy agonist. At micromolar concentrations, dopamine also acts as a partial-efficacy agonist on 5-HT2A receptors in HEK293 cells. Like 5-HT, dopamine also induces receptor-internalization in these cells, although at significantly higher concentrations than 5-HT. Interestingly, if the receptors are first sensitized or "primed" by subthreshold concentrations of 5-HT, then dopamine-induced internalization occurs at concentrations approximately 10-fold lower than when dopamine is used alone. Furthermore, unlike 5-HT-mediated internalization, dopamine-mediated receptor internalization, alone, or after sensitization by 5-HT, does not depend on PKC. Dopamine-internalized receptors recycle to the surface at rates similar to those of 5-HT-internalized receptors. Our results suggest a previously uncharacterized role for dopamine in the direct activation and internalization of 5-HT2A receptors that may have clinical relevance to the function of serotonergic systems in anxiety, depression, and schizophrenia and also to the treatment of these disorders.


Analysis of the transverse and the longitudinal pseudodiffusion of CO2 in sub- and supercritical states: a molecular-dynamics analysis.
We have performed molecular-dynamics simulations of CO(2) system along the gas-liquid coexistence curve and on the isochore 94.22 cm(3) mol(-1) (which corresponds to the critical isochore). The calculation has been carried out in order to analyze the diffusion of CO(2) and particularly to figure out how the diffusion coefficient may be decomposed along the molecular axes. This makes it possible to analyze the anisotropy of the diffusion along these axes and to shed light on the microscopic changes which accompany such behavior. This anisotropy is traced back to the effect of the translation-rotation coupling (TRC) along the molecular axes. Along the liquid-gas coexistence curve, the pseudolongitudinal diffusion is found to be more rapid than the transverse one. The opposite trend is found along the isochore 94.22 cm(3) mol(-1). The role of the local structure was explored by calculating intermediate scattering function and the autocorrelation functions for the forces acting along the molecular axes. It is shown that the strength of the TRC effect is correlated to the difference between the relaxation times of the local structure, that of the reorientation along the molecular axes, and that of the translational motion. The analysis of the correlation time and the average mean square force along the longitudinal and transverse directions confirms the anisotropy of the local environment that determines the translational dynamics of a molecule.


A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives.
Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.


Cuticular Waxes of Arabidopsis thaliana Shoots: Cell-Type-Specific Composition and Biosynthesis.
It is generally assumed that all plant epidermis cells are covered with cuticles, and the distinct surface geometries of pavement cells, guard cells, and trichomes imply functional differences and possibly different wax compositions. However, experiments probing cell-type-specific wax compositions and biosynthesis have been lacking until recently. This review summarizes new evidence showing that Arabidopsis trichomes have fewer wax compound classes than pavement cells, and higher amounts of especially long-chain hydrocarbons. The biosynthesis machinery generating this characteristic surface coating is discussed. Interestingly, wax compounds with similar, long hydrocarbon chains had been identified previously in some unrelated species, not all of them bearing trichomes.


A Comparative Study on the Psychological Health of Frontline Health Workers in Wuhan Under and After the Lockdown.
Background: The coronavirus disease-2019 (COVID-19) outbreak and a 3-month lockdown of Wuhan may have had a long-term impact on the mental health of frontline healthcare workers (HWs). However, there is still a lack of comparative studies on the mental health of front-line HWs in the initial phase of the lockdown and 1 month after the lifting of the lockdown. Methods: We recruited 1717 HWs during the initial phase of the lockdown and 2214 HWs 1 month after the lifting of the lockdown, and their baseline characteristics and psychiatric health in these two phases were compared. Furthermore, Pearson's Chi-square test and multivariate logistic regression analysis were used to determine the possible risk factors associated with depressive symptoms in the front-line HWs. Results: Compared with the initial phase of the lockdown, the proportion of HWs with anxiety symptoms and stress decreased, while the proportion of HWs with depressive symptoms increased a month after the lifting of the lockdown. Male sex, exercise habit, comorbidities, and having family members or relatives with suspected or confirmed COVID-19 infection were significantly related to the increased incidence of depressive symptoms during the initial phase of the lockdown. Comorbidities, negative effect of media coverage, working >4 days a week, lower annual household income, and deteriorating relationships with family members were associated with depressive symptoms a month after the lifting of the lockdown. Conclusion: The increased proportion of HWs with depressive symptoms 1 month after the lifting of the lockdown suggested that mental health of front-line HWs should be a top-priority issue, not only during, but also after the pandemic.


Kinetic models for enzymic cellulose degradation in aqueous two-phase systems.
Cellulose materials can readily be degraded into cellobiose and glucose by hydrolysis of the enzymes cellulase and beta-glucosidase in aqueous media. Product inhibition does, however, retard the reaction rate and reduce productivity. This may be avoided by carrying out the degradation of cellulose in an aqueous two-phase system, which permits the enzymes and the substrate to be partitioned to one phase and the products to be extracted into a second phase. In addition, two-phase systems also allow recycling of the enzymes. Here, three models previously developed for "one-phase" enzymic degradation are compared to data from enzymic degradation in an aqueous two-phase system. The models tested agreed relatively well with batch experiments during a period of 200 h. For one of the models tested, continuous degradation also gave accurate agreement.


Polyunsaturated fatty acids and ethanol.
Ethanol exposure leads to a loss in membrane polyunsaturated fatty acids (PUFA). It is proposed that polyunsaturated species of phospholipids are not randomly distributed, but are concentrated in the cytosolic leaflets of the plasma membrane and are preferentially associated with membrane proteins. These lipids affect the physical state of environments surrounding membrane proteins and thereby serve to regulate many cellular functions. Disruption of these environments may occur even when a small percentage of total polyunsaturates is lost due to ethanol exposure. One possible mechanism of ethanol-induced polyunsaturate loss may be activation of a phospholipase A2 enzyme which is selective for these species of phospholipids. Fatty acids released would stimulate the production of prostaglandins and/or leukotrienes. Similarly, the released docosahexaenoate can be metabolized by rat brain to leukotriene-like compounds which are biologically active in smooth muscle systems. This metabolism is stimulated by ethanol in human platelets, in vitro.


The relationship between lower limb maximal and explosive strength and change of direction ability: Comparison of basketball and tennis players, and long-distance runners.
Change-of-direction (CoD) ability is an important determinant of athletic performance. Muscle strength is among the most important determinants of CoD ability. However, previous studies investigating the relationship between CoD ability and muscle strength focused mostly on flexor and extensor muscle groups, or used multi-joint exercises, such as jumps, squats or mid-thigh pull. The purpose of the present study was to investigate the relationship between CoD ability and strength of ankle, knee, hip and trunk maximal and explosive strength. The participants (n = 327), consisting of male and female basketball players, tennis players and long-distance runners completed isometric strength assessments and CoD testing (90° and 180° turn tests). The times of both CoD tests were associated with muscle strength (peak torques and the rate of torque development variables), with correlation coefficients being mostly weak to moderate (r = 0.2-0.6). Strength variables explained 33%, 62% and 48% of the variance in the 90° turn task, and 42%, 36% and 59% of the variance in the 180° turn task, in basketball players, long-distance runners and tennis players, respectively. Hip and trunk muscle strength variables were the most prevalent in the regression models, especially hip adduction and abduction strength. Our results suggest that the strength of several lower limb muscles, in particular of the hip abductors and adductors, and trunk muscles, but also hip rotators, extensors and flexors, as well as knee and ankle flexors and extensors should be considered when aiming to improve CoD performance.


Nuclear targeted suppression of NF-kappa B activity by the novel quinone derivative E3330.
The activation of NF-kappa B consists of at least three steps: degradation of I kappa B alpha, translocation of NF-kappa B into the nucleus, ai post-translational modification of NF-kappa B (e.g., phosphorylation of p65). In the present study, we found that a novel quinone derivative E3330 selectively inhibited NF-kappa B-mediated gene expression without affecting any of these steps. E3330, when included in the culture medium, suppressed NF-kappa B DNA-binding activity in PMA-induced Jurkat cell nuclear extracts, suggesting that the inhibition by E3330 of NF-kappa B-mediated gene expression was due to its ability to suppress NF-kappa B DNA-binding activity. Fractionation of the nuclear extracts by column chromatography revealed that a nuclear factor enhanced NF-kappa B DNA-binding activity and that this enhancing activity was interrupted after treatment with E3330. Moreover, a major polypeptide with a molecular mass of 40 kDa was found to be in the highly purified fraction containing the NF-kappa B-enhancing activity and predominantly bind E3330. Taken together, these results suggest that the NF-kappa B activity, after dissociation from I kappa B, is enhanced by a nuclear factor that is active irrespective of PMA treatment, and the nuclear factor-mediated enhancement is selectively inhibited by E3330. Thus, we conclude that E3330 may belong to a novel class of anti-NF-kappa B drugs.


Characterization and regulation of somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) receptors on cultured pig Leydig cells. Effects of Sm-C/IGF-I on luteotropin receptors and steroidogenesis.
We have characterized somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) receptors in cultured pig Leydig cells by binding and cross-linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell were 1.8 +/- 0.2 X 10(-9) M and 12,200 +/- 3200 respectively. Under reducing conditions, disuccinimidyl suberate cross-linked 125I-Sm-C to one receptor complex with apparent Mr = 120,000. Continuous treatment of Leydig cells with increasing concentrations of human chorionic gonadotropin (hCG) for 48 h resulted in a dose-dependent (ED50 0.05 nM) increment in IGF type I receptors (2.5-3-fold increase). Conversely, treatment of Leydig cells for 48 h with increasing concentrations of Sm-C/IGF-I produced a 3-4-fold increase in hCG receptors. This effect was dose-dependent (ED50 = 7 ng/ml). Sm-C/IGF-I treatment also enhanced Leydig cell responsiveness to hCG for both cAMP (6-fold) and testosterone (8-fold). Moreover the stimulatory effects of Sm-C/IGF-I on cells cultured either in the absence or presence of 5% human serum from an hypopituitary patient were inhibited by anti-(Sm-C/IGF-I) antibodies. Taken together these results not only show that Leydig cells must be considered as targets for Sm-C/IGF-I, but also lend support to the possibility that Sm-C/IGF-I plays a role in the regulation of Leydig cell function. Moreover, they suggest that Sm-C/IGF-I might be responsible for the delayed puberty observed in some patients with isolated growth hormone deficiency.


Nontuberculous mycobacteria.
Nontuberculous mycobacteria are identified in almost half of the cultures reported positive for mycobacteria in clinical laboratories in the United States. While many represent saprophytic colonization or laboratory contamination, a significant number of these organisms are the agents of disease. Such organisms can be the cause of pulmonary, soft tissue, cutaneous and lymphatic infections, keratitis, osteomyelitis, postsurgical infection, endocarditis and disseminated disease.


Xenopus Xpat protein is a major component of germ plasm and may function in its organisation and positioning.
In many animals, including Drosophila, C. elegans, zebrafish and Xenopus, the germ line is specified by maternal determinants localised in a distinct cytoplasmic structure called the germ plasm. This is consists of dense granules, mitochondria, and specific localised RNAs. We have characterised the expression and properties of the protein encoded by Xpat, an RNA localised to the germ plasm of Xenopus. Immunofluorescence and immunoblotting showed that this novel protein is itself a major constituent of germ plasm throughout oogenesis and early development, although it is also present in other regions of oocytes and embryos, including their nuclei. We found that an Xpat-GFP fusion protein can localise correctly in cultured oocytes, in early oocytes to the 'mitochondrial cloud', from which germ plasm originates, and in later oocytes to the vegetal cortex. The localisation process was microtubule-dependent, while cortical anchoring required microfilaments. Xpat-GFP expressed in late stage oocytes assembled into circular fields of multi-particulate structures resembling endogenous fields of germ plasm islands. Furthermore these structures could be induced to form at ectopic sites by manipulation of culture conditions. Ectopic Xpat-GFP islands were able to recruit mitochondria, a major germ plasm component. These data suggest that Xpat protein has an important role in Xenopus germ plasm formation, positioning and maintenance.


An evaluation of auditory exostoses in 621 prehistoric human skulls from coastal Brazil.
Auditory exostoses are bone anomalies located on the floor of the external auditory canal. They frequently develop in individuals who participate in water sports and other aquatic activities. Their etiology is probably multifactorial; development seems to be triggered by regular exposure to cold water as well as to low air temperatures and/or cold winds. The presence ofauditory exostoses has been recorded in human skull fossils that date back approximately 250,000 years. We conducted a study of auditory exostoses in 621 skulls of adult humans who had been part of a marine-dependent population that lived on the Brazilian coast between 5400 and 800 years ago. The overall frequency of exostoses was 22%, but there was a great variance among different subgroups (0 to 56%). In this article, we propose some possible explanations for this variance. We also hope that our study will stimulate multidisciplinary research aimed at deciphering the intricate bony messages contained in cryptic archaeologic remains.


Rapid decay of transthoracic echocardiography skills at 1 month: A prospective observational study.
Focused transthoracic echocardiography (FTTE) is an emerging tool in the management of critically ill patients, but the lack of adequate training models has limited the expansion of this technology. Although basic FTTE training courses have been shown to be sufficient in developing echocardiography skills, limited data exist regarding skill retention. In an effort to develop an adequate FTTE training model, we sought to determine the degree of skill retention after FTTE training. A prospective, observational study. An academic center. Surgical residents and medical students: 31 subjects were enrolled from February to June 2016. Participants underwent a 2-hour FTTE course including didactics and a hands-on session measuring ejection fraction of left ventricle (LV) and inferior vena cava (IVC) diameter. Written knowledge and performance examinations applying FTTE were conducted before the course, immediately after, and at 1- and 3-month intervals, which were evaluated on a 0 to 9 scale and analyzed with paired t-tests. Performance examination scores obtaining the LV and IVC views preinitial and postinitial training increased from 1.7 to 6.5 (LV) and from 2.0 to 6.8 (IVC) (p < 0.01), decreased to 5.0 and 4.8, respectively, at 1 month (posttraining vs 1 month, p < 0.01), and did not significantly change at 3 months (5.4 and 5.0, respectively). Written examination scores increased from 42% to 62% (pretraining vs posttraining, p < 0.01), decreased to 48% in 1 month (posttraining vs 1 month, p < 0.01), and further decreased to 34% at 3 months (1 month vs 3 month, p < 0.01). Although a short training course appears sufficient to impart basic FTTE skills and knowledge, skills are significantly decayed at 1 month and knowledge continually decreases at 1 and 3 months. Future FTTE training models should consider the rapid degradation of knowledge and skills in determining frequency of refresher training and ongoing evaluation.


Effects of synbiotics on immunity and disease resistance of narrow-clawed crayfish, Astacus leptodactylus leptodactylus (Eschscholtz, 1823).
The aim of this study was to evaluate the effects of prebiotics (mannanoligosaccharide and xylooligosaccharide), probiotics (Enterococcus faecalis and Pediococcus acidilactici) and synbiotics for 126 days on the immune responses, hemolymph indices, antioxidant enzymes, and biological responses after a 48-hour Aeromonas hydrophila exposure of sub-adult crayfish (11.45 ± 1.87 g). Most antibacterial activities were observed in the shell mucus of crayfish fed a diet containing xylooligosaccharide + E. faecalis and mannanoligosaccharide + Pediococcus acidilactici against Nocardia brasilience and Vibrio harveyi (p < 0.05). Feeding crayfish a xylooligosaccharide + E. faecalis diet increased protein levels and the activities of alkaline phosphatase and lysozyme in the shell mucus after the feeding trial and 48 h after the A. hydrophila-injection challenge (p < 0.05). The highest ratio of the lactobacillus count to the total viable count was observed in synbiotic diets (p < 0.05). Feeding crayfish a xylooligosaccharide + E. faecalis diet increased the growth rate and the resistance to the A. hydrophila-injection challenge (p < 0.05). These results revealed that feeding crayfish with synbiotic diets was more effective than a single administration with prebiotics and probiotics.


The household garbage in the western coast region of Turkey and its relationship with the socio-economic characterstics.
The aim of this study is to detect the daily amount of household garbage generated from districts within the limits of municipality of Aydin, the amount and contents of recyclable materials and to evaluate the effect of socioeconomic state. In this cross sectional survey, garbage was collected for one day from all of the districts, weighed both totally and after separation into groups. The districts were assessed according to literacy, drinking water sources and toilet indexes. For each district, three indexes were calculated viz. literacy, water and sewage index. Points between 1-3 were given and by adding points of each index, socioeconomic development (SED) score was calculated for each district. The daily amount of garbage produced was 0.91 +/- 0.74 kg/person and recyclable material was 0.08 +/- 0.13 kg/person (6.4%). A significant corelation was found between SED point and amount of recyclable materials (p < 0.05). There was a positive, strong and significant correlation between workplaces in the districts and recyclable garbage (r = 0.597, p < 0.05). In further analysis, number of workplaces increased the daily amount of garbage by 9.9 times (p < 0.001; 95% confidence Interval: 4.538-15.189), whereas population 0.6 times (p < 0.05; 95% confidence interval: 0.407-0.708).


[Clinical study of porous gelatin sphere (YM 670) in transcatheter arterial embolization].
A clinical study on the use of porous gelatin particles(sterile gelatin embolization material, YM 670, Gelpart) in transcatheter arterial embolization (TAE) was performed in patients with hepatocellular carcinoma, and the efficacy (embolization,anti-tumor effect, recanalization and operationality) and safety (tolerability) were studied. An additive agent comprising porous gelatin particles and low osmolarity contrast media was administered peripherally through a catheter into the hepatic artery proper of 63 patients with hepatocellular carcinoma. Good hepatic arterial embolization was confirmed in all cases (embolization: 100%), and a tumor necrosis effect was obtained in most cases (35/62 patients, 56.5%). Moreover, operationality was assessed as "highly easy to use" or "easy to use" in all cases. Frequencies of adverse events in which a relationship to TAE was not excluded and abnormalities of clinical laboratory data were high at 71.4% and 9 8.4%, respectively. The most common adverse reactions were pyrexia, abdominal pain, queasiness and blood pressure increase;abnormalities in clinical laboratory data included hepatic function with increased AST (GOT), increased ALT (GPT), decreased cholinesterase, increased LDH and increased total bilirubin. These adverse reactions and abnormalities in clinical laboratory data, however, were transient and attributed to the TAE procedure itself, and no adverse reactions related to YM 670 as an embolic material were observed. In addition, with regard to tolerability (safety), the treatment was assessed as suitable for use in all the present cases.


The analgesic effects of preemptive gabapentin in patients undergoing surgery for brachial plexus injury--a preliminary study.
There are reports indicating that gabapentin may have place in the treatment of postoperative pain. No study has evaluated the effects of gabapentin on acute, postoperative pain in patients undergoing surgery for brachial plexus injuries. In this preliminary study, we evaluated gabapentin as preemptive analgesic for intraoperative period and during the acute postoperative period at rest and during movement. Twenty consecutive adult patients undergoing surgery for brachial plexus injury were enrolled for the study. Patients randomly received either oral gabapentin 800 mg or placebo capsules 2 hours before surgery. General anesthesia was induced and maintained with propofol, at bispectral index value between 40 and 60. Intraoperative fentanyl and propofol requirements were noted. Postoperatively, all patients were alert and pain was assessed using visual analog scale (VAS) for 24 hours, both during rest and movement. Whenever VAS score was more than 50 or on patients' demand, ketorolac 30 mg was given as rescue analgesic. The demographics, duration of surgery, and propofol consumption in both groups were comparable. Intraoperative and postoperative heart rate and mean blood pressure were also comparable. Significant difference was noted in intraoperative fentanyl consumption (P=0.03), total dose of rescue analgesic (P=0.004), and VAS score at rest and movement, between the 2 groups; less in gabapentin group as compared with placebo group (P=0.01 and 0.04, at rest and movement, respectively). A single oral dose of gabapentin 800 mg, as preemptive analgesic in patients undergoing surgery for brachial plexus injury is found to be an effective adjunct to intraoperative and postoperative pain. Pain is reduced not only at rest but also during movement.


Evidence for the implication of endogenous vasopressin in cardiovascular response to central alpha-adrenoceptor stimulation.
To determine the role of endogenous vasopressin (AVP) in cardiovascular response to central alpha-adrenoceptor stimulation, alpha 1-agonist methoxamine or alpha 2-agonist clonidine was administered intracerebroventricularly (ICV) to conscious Long-Evans (LE) rats as well as Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI). In LE rats, ICV methoxamine increased blood pressure (BP) and decreased heart rate (HR), while ICV clonidine caused initial hypertension associated with bradycardia followed by prolonged hypotension with tachycardia. In DI rats, however, ICV methoxamine had no detectable effect on BP and HR, whereas ICV clonidine produced greater hypotension than in LE rats together with less initial bradycardia. Plasma levels of AVP increased 5-15 fold by methoxamine but did not change by clonidine. The intravenous (IV) but not ICV pretreatment with AVP vascular receptor antagonist d (CH2)5 Tyr (Me) AVP significantly attenuated the cardiovascular effects of methoxamine in LE rat, while neither IV nor ICV pretreatment with AVP antagonist modulated the cardiovascular effects of clonidine. These results provide the evidence for the implication of endogenous AVP in the cardiovascular response to central stimulation of alpha-adrenoceptors.


International regulatory landscape and integration of corrective genome editing into in vitro fertilization.
Genome editing technology, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas, has enabled far more efficient genetic engineering even in non-human primates. This biotechnology is more likely to develop into medicine for preventing a genetic disease if corrective genome editing is integrated into assisted reproductive technology, represented by in vitro fertilization. Although rapid advances in genome editing are expected to make germline gene correction feasible in a clinical setting, there are many issues that still need to be addressed before this could occur. We herein examine current status of genome editing in mammalian embryonic stem cells and zygotes and discuss potential issues in the international regulatory landscape regarding human germline gene modification. Moreover, we address some ethical and social issues that would be raised when each country considers whether genome editing-mediated germline gene correction for preventive medicine should be permitted.


Audiovisual distraction as an anxiety-minimising adjuvant to regional anaesthesia in adult limb surgery: a service evaluation using patient reported experience measures.
Audiovisual distraction (AVD) is an expanding anxiety-minimising technique for patients undergoing surgery under regional anaesthesia (RA). We evaluated patient satisfaction with AVD in the setting of conscious RA for limb surgery using patient reported experience measures (PREMs). Service evaluation using PREMs, via standardised post-operative patient questionnaire, in a single tertiary referral centre for orthopaedic and plastic surgery over an 18-month period. Outcome measures included impact of AVD on peri-operative anxiety, comfort, satisfaction and comparison with previous general anaesthesia (GA) experiences. 50 adult patients undergoing elective limb surgery under RA ± sedation were provided with a wifi-enabled tablet device peri-operatively and completed a post-operative questionnaire regarding their AVD experience. 100% were satisfied with AVD and would recommend to others. 78% were anxious before or during the procedure, of which 97% felt that AVD improved their anxiety levels. Of the 94% with previous experience of GA, 89% reported a 'better' experience with RA + AVD. PREMs regarding AVD were encouraging and lay a foundation for further clinical service development and research into incorporation of this technique for appropriate RA patient groups. Our findings are particularly relevant in the COVID-affected era of anaesthesia as RA benefits and strategies to minimise anxiety are reappraised.


Isolation and characterization of human peripheral blood CD4+ T cell clones expressing gamma delta T cell receptors.
Rare T cell clones bearing both CD4 and gamma delta T cell receptors (TcR gamma delta) were obtained from human peripheral blood by cell sorting using anti-CD4 and anti-TCR delta 1 antibodies. All the clones established were reactive with anti-TcR gamma delta 1 antibody, whereas only about 20% of the clones showed reactivity with anti-delta TCS1 antibody. Unlike most CD4+ T cells bearing TcR alpha beta, all the clones tested showed lectin-dependent and anti-CD3 antibody-redirected cytolytic activity. About 60% of the clones exhibited natural killer cell-like activity. Immunoprecipitation analysis of TcR gamma delta showed that each clone expressed either a disulfide-linked or non-disulfide-linked heterodimer consisting of 37-44-kDa TcR gamma and TcR delta chains.


3,6-Dihydroxy-2-(11-phenylundecanoyl)cyclohex-2-en-1-one from Virola venosa bark.
The structure of the title compound, C23H32O4, an arylalkanone isolated from the petroleum ether fraction of the ethanol extract of the bark of Virola venosa, has been established by NMR spectroscopy and, for the first time, by X-ray structure analysis. Two independent molecules of the same enantiomer are present in the unit cell. Both molecules exhibit an intramolecular hydrogen bond, which can be correlated with a rare signal observed at 18.28 p.p.m. in the 1H NMR spectrum. The packing, in space group P1, is determined by a pseudo-center of symmetry leading to a short intermolecular contact, which is present in one molecule but does not occur in the other. As a consequence, the O-C-C-O torsion angles [-16.9 (3) and -12.7 (3) degrees ] through the ketone and its adjacent hydroxy group are significantly different in the two molecules.


[MR spectroscopy in acute brain infarction: differentiation of infarcted and non-infarcted areas].
Two cases of brain infarction were studied using multivoxel proton MR spectroscopy (MRS). MRS of both cases clearly demonstrated an increased level of lactate and decreased N-acetylaspartate (NAA), resulting in a high lactate/NAA ratio (LNR). Case 1 without thrombolysis therapy revealed that the area where LNR was less than 1.0 did not develop to infarction. This was also confirmed by MRS of case 2, who received an interventional reperfusion 4 hours after onset. In acute stags of brain infarction, on LNR greater than 1.0 on H-MRS may predict the margin of the infarcted region. Elevation of lactate in the non-infarcted cerebral hemisphere has not been reported before, and farther evaluation is necessary.


Oral hygiene instructions and dietary sugar advice received by adolescents in 1989 and 1997.
The aim of this study was to find out how commonly adolescents receive oral hygiene instructions and dietary sugar advice in the Finnish public oral health care system and whether there have been any changes between 1989 and 1997. The data were collected as part of a nationwide research program, the Adolescent Health and Lifestyle Survey. Since 1977, a questionnaire has been sent every second year to a representative sample of 12-, 14-, 16- and 18-year-old Finns eligible for free comprehensive oral health care. The sample size was 3105 in 1989 and 8390 in 1997. Almost all adolescents (95-96%) had visited a dentist during the last 2 years. In all age groups, boys reported having received tooth cleaning instructions during their dental visit more often than girls did (40%/35%). There was only a minor decrease in instructions received between 1989 and 1997. Boys and those who brushed their teeth once a day or less often were the most likely to receive instructions in 1997. Only one-fifth of adolescents reported having received dietary sugar advice, and there was a slight decrease between 1989 and 1997. In 1997, the groups of adolescents most likely to be advised were 12-16-year-old-boys, those using sweets daily and those living in Central Finland. Oral health instructions were only given to a minority of adolescents. The targeting of adolescents with health-damaged behavior is therefore important.


Neighborhood Poverty and 9-1-1 Ambulance Response Time.
Are 9-1-1 ambulances relatively late to poorer neighborhoods? Studies suggesting so often rely on weak measures of neighborhood (e.g., postal zip code), limit the analysis to particular ambulance encounters (e.g., cardiac arrest responses), and do little to account for variations in dispatch priority or intervention severity. We merged EMS ambulance contact records in a single California county (n = 87,554) with tract-level data from the American Community Survey (n = 300). After calculating tract-level median ambulance response time (MART), we used ordinary least squares (OLS) regression to estimate a conditional average relationship between neighborhood poverty and MART and quantile regression to condition this relationship on 25th, 50th, and 75th percentiles of MART. We also specified each of these outcomes by five dispatch priorities and by three intervention severities. For each model, we estimated the associated changes in MART per 10 percentage point increase in tract-level poverty while adjusting for emergency department proximity, population density, and population size. Our study produced three major findings. First, most of our tests suggested tract-level poverty was negatively associated with MART. Our baseline OLS model estimates that a 10 percentage point increase in tract-level poverty is associated with almost a 24 s decrease in MART (-23.55 s, 95% confidence interval [CI] -33.13 to -13.98). Results from our quantile regression models provided further evidence for this association. Second, we did not find evidence that ambulances are relatively late to poorer neighborhoods when specifying MART by dispatch priority. Third, we were also unable to identify a positive association between tract-level poverty and MART when we specified our outcomes by three intervention severities. Across each of our 36 models, tract-level poverty was either not significantly associated with MART or was negatively associated with MART by a magnitude smaller than a full minute per estimated 10 percentage point increase in poverty concentration. Our study challenges the commonly held assumption that ambulances are later to poor neighborhoods. We scrutinize our findings before cautiously considering their relevance for ambulance response time research and for ongoing conversations on the relationship between neighborhood poverty and prehospital care.


Neuroprotective effect of Lovastatin on motor deficit induced by sciatic nerve crush in the rat.
Following severe peripheral nerve injury (PNI), regeneration is often insufficient and functional recovery is incomplete. Any agents that limit the spread of neural tissue damage may enhance the nerve regeneration. In this regard, statins have been shown to have neuroprotective properties. We investigated the effects of Lovastatin against sciatic nerve crush injury in male Wistar Rats. Lovastatin or vehicle was given parenteraly to rats for 7 days postoperative. In Lovastatin treatment groups, a single dose of agent (2 and 5mg/kg) was administered daily. The control group was given vehicle in the same manner. The rats were subjected to crush injury in the left sciatic nerve with non-serrated clamp for 30s. Behavioral, electrophysiological and morphological alterations were evaluated during the experimental period. Results showed that Lovastatin in a dose of 5mg/kg could significantly (P < 0.05) accelerate regeneration process and functional recovery. Also results demonstrated that morphometric parameters such as mean axonal number and myelin thickness were significantly higher in Lovastatin (5mg/kg) treatment groups compared to controls (P < 0.05). These findings suggest that a short-term course treatment with Lovastatin can protect against sciatic nerve injury. Findings indicate that postoperative administration of Lovastatin led to accelerate regeneration process and motor function recovery in nerve crush model in rats. This effect might be due to the anti-inflammatory, immunomodulatory or anti-oxidative properties of Lovastatin. It is clear that more research is needed to confirm these findings.


Evaluation and Exploration on the Effect of the Management of Chronic Obstructive Pulmonary Disease in Rural Areas through an Internet-Based Network Consulting Room.
This study aims to improve the management quality of chronic obstructive pulmonary disease (COPD) in rural areas. Two hundred forty discharged COPD patients were divided into an intervention group and a control group. In the intervention group, 120 patients established contact with doctors through the network consulting room, i.e., the doctor's mobile platform, and were managed through video, voice, and text by the doctors, kept close contact with the doctors after discharge (education, consultation), and received electronic prescriptions, and drugs were sent to the patients' door by online retailers. The patients in the control group were managed in the traditional manner. One year later, the predicted forced expiratory volume in 1 s (FEV1)%, FEV1/forced vital capacity (FVC), and CAT scores and the number of rehospitalized patients were compared between these 2 groups. After 1 year of follow-up, the predicted FEV1% and the FEV1/FVC ratio were significantly higher in the intervention group than in the control group (p < 0.05). CAT scores were lower for patients in the intervention group than for those in the control group after 1 year of follow-up (p < 0.05). After 1 year of follow-up, 22 (18.33%) patients were rehospitalized in the intervention group and 58 (48.33%) patients were rehospitalized in the control group (p < 0.05). Doctors can improve the quality of life of patients with COPD and reduce the number of rehospitalizations through use of the network consulting room.


[The best cuff for measuring arterial pressure].
Hypertension prevention, detection, follow-up and medication adjustment depend on valid blood pressure measurement. Many factors should be taken into consideration to get accurate blood pressure readings: the blood pressure measurement method, the equipment used and the patient preparation. This column will focus on the importance of the cuff for blood pressure measurement.


Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta.
Nucleosides, organic acids, and amino acids separated from Morchella esculenta are well known for their nutritional value and flavor. However, how to increase their content in a better way has been a challenge. In this study, the effect of adding jujube kernel on the active components of M. esculenta was investigated by untargeted metabolomics using UPLC-MS/MS. A total of 1,243 metabolites were identified, of which 262 metabolites (21.078%) were organic acids and derivatives, 245 metabolites (19.71%) were lipids and lipid-like molecules, and 26 metabolites (2.092%) were nucleosides, nucleotides, and analogues. Subsequently, differential metabolites between groups were screened by the orthogonal partial least squares-discriminant analysis model, which showed that 256 metabolites were identified as significantly different for the positive ion model and 149 for the negative ion model. Moreover, significant differential metabolites (VIP > 1, P < 0.05) in annotation of kyoto encyclopedia of genes and genomes pathway were investigated, which showed that ABC transporters were the most commonly observed transporters, followed by pyrimidine metabolism and purine metabolism. The results indicated that the main components of jujube kernel might be conducive to the accumulation of nucleoside organic acids and amino acid metabolites in M. esculenta. These results provide important information for the understanding of more suitable way for cultivation of M. esculenta.


Medullasin enhances human natural killer cell activity.
Medullasin, a new serine protease found in bone marrow cells, increased markedly human natural killer cell activity. Whereas the natural killer cell activity measured immediately after the treatment with medullasin remained almost on the same level as the control, an incubation at 37 degrees C for several hours increased markedly the natural killer cell activity of the lymphocytes treated with medullasin. Enhancement of the natural cytotoxicity was caused by the treatment with physiologic concentrations of the protease (5-20 micrograms/ml). Inhibitors of medullasin such as phenylmethylsulfonyl fluoride and elastatinal prevented the activation of natural cytotoxicity. Depletion of lymphocytes bearing Fc receptors for IgG abolished the enhancement of natural killer cell activity by medullasin. Interferon activity was not detected in the supernatant of lymphocyte cultures stimulated with medullasin. The medullasin enhanced further the natural killer cell activity of lymphocytes stimulated with interferon. Medullasin activity was detected neither in unstimulated nor stimulated (by concanavalin A or phytohemagglutinin) human lymphocytes. The protease was released easily from human mature granulocytes into culture medium. It is considered from these results that the level of human natural killer cell activity is regulated by medullasin released by mature granulocytes.


Fast 2D phantom dosimetry for scanning proton beams.
A quality control system especially designed for dosimetry in scanning proton beams has been designed and tested. The system consists of a scintillating screen (Gd2O2S:Tb), mounted at the beam-exit side of a phantom, and observed by a low noise CCD camera with a long integration time. The purpose of the instrument is to make a fast and accurate two-dimensional image of the dose distribution at the screen position in the phantom. The linearity of the signal with the dose, the noise in the signal, the influence of the ionization density on the signal, and the influence of the field size on the signal have been investigated. The spatial resolution is 1.3 mm (1 s.d.), which is sufficiently smaller than typical penumbras in dose distributions. The measured yield depends linearly on the dose and agrees within 5% with the calculations. In the images a signal to noise ration (signal/1 s.d.) of 10(2) has been found, which is in the same order of magnitude as expected from the calculations. At locations in the dose distribution possessing a strong contribution of high ionization densities (i.e., in the Bragg peak), we found some quenching of the light output, which can be described well by existing models if the beam characteristics are known. For clinically used beam characteristics such as a Spread Out Bragg peak, there is at most 8% deviation from the NACP ionization chamber measurements. The conclusion is that this instrument is a useful tool for quick and reliable quality control of proton beams. The long integration-time capabilities of the system make it worthwhile to investigate its applicability in scanning proton beams and other dynamic treatment modalities.


Treatment for substance abuse in Australia: a comparison of public and private programs.
Alcohol and drug abuse is a major problem in Australia and caused over 4000 deaths in 1998 alone. The national policy for reducing the harmful consequences of drug and alcohol use focuses on decreasing the production and supply of drugs, reducing the demand for drugs including a focus on abstinence in treatment, and minimizing the harm to individuals and communities. This research examines substance abuse treatment in Australia, and identifies similarities and differences in funding, philosophy, purpose, and strategies between public and private treatment programs. Interviews of 21 treatment program directors in Sydney and Melbourne were done, using a valid and reliable semi-structured interview guide. Nine public, not-for-profit programs primarily focused on consultation to medical providers, detoxification, outpatient counseling, and harm minimization including methadone treatment and needle exchange. Rehabilitation, prevention, and/or research were objectives of a limited number. Twelve private, non-governmental programs primarily provided abstinence-based treatment in a variety of settings. Some for-profit programs, funded by insurance, provided three to four weeks inpatient care, usually with outpatient follow-up. Not-for-profit programs provided residential treatment in a therapeutic community over a period of 6 months to 2 years. Still others (both profit and not-for-profit) provided methadone treatment or outpatient treatment. Four were church related and six received funding through government contracts, social security illness benefits, and housing assistance. The general lack of structured rehabilitation programs seemed to be the greatest weakness of the Australian public programs. A low percentage of patients completing detoxification entered counseling, and studies were not available to show the outcomes of detoxification without follow-up. The availability of consultations to hospitals and health care practitioners seemed to be an excellent advantage, but the lack of structured SAT beyond detoxification may have minimized that advantage. Nurses were involved in a variety of roles in Australia, and six of the program directors or managers we interviewed were nurses. Nurses were usually in clinical roles or management roles, rather than counseling roles.


Tipranavir: a new protease inhibitor for the pediatric population.
Highly active antiretroviral therapy can provide sustained viral suppression and a beneficial immunological response in both antiretroviral-naive and -experienced pediatric patients infected with HIV. While there have been many antiretroviral studies in adults infected with HIV, considerably less information is available in similar HIV-infected pediatric or adolescent patients. Tipranavir, a new-generation protease inhibitor approved for use in adults with resistant HIV strains, has recently been studied in HIV-infected children and adolescents. In this article, we summarize available pharmacokinetic, safety, tolerability and efficacy data obtained from children and adolescents treated with a pediatric tipranavir formulation.


Post-translational Acetylation Control of Cardiac Energy Metabolism.
Perturbations in myocardial energy substrate metabolism are key contributors to the pathogenesis of heart diseases. However, the underlying causes of these metabolic alterations remain poorly understood. Recently, post-translational acetylation-mediated modification of metabolic enzymes has emerged as one of the important regulatory mechanisms for these metabolic changes. Nevertheless, despite the growing reports of a large number of acetylated cardiac mitochondrial proteins involved in energy metabolism, the functional consequences of these acetylation changes and how they correlate to metabolic alterations and myocardial dysfunction are not clearly defined. This review summarizes the evidence for a role of cardiac mitochondrial protein acetylation in altering the function of major metabolic enzymes and myocardial energy metabolism in various cardiovascular disease conditions.


Effects of dextran infusion on cardiac output, oxygen delivery, and oxygen utilization in piglets during the first month of life.
We determined the effects of volume infusion on cardiac output, oxygen delivery (Do2), oxygen consumption (Vo2), and oxygen extraction (O2 extr) in piglets at ages 5 to 14 days and 3 to 5 wk. Eighteen piglets were anesthetized, intubated, and mechanically ventilated. Six piglets (5 to 14 days old) and six piglets (3 to 5 wk old) received iv dextran (MW 70,000 daltons; 30 to 40 ml/kg) sufficient to raise mean left atrial pressure (LAP) from approximately 4 to 15 mm Hg over 30 min. Six piglets received 0.9% NaCl at 4 ml/kg.h to maintain LAP constant at 4 mm Hg over a 30-min period. All piglets receiving dextran had increased cardiac output (mean elevation 39 +/- 16 [SD]%; range +19% to +73%; p less than .005). This response was mediated entirely by an elevation in stroke volume, as heart rate did not change significantly. However, all piglets receiving dextran reduced Hgb concentration (10.1 +/- 1.5 to 7.5 +/- 1.4 g/dl, p less than .001), a decrease which completely offset the increase in cardiac output. Consequently, Do2 did not increase after dextran infusion (17.4 +/- 1.8 to 18.4 +/- 2.8 ml/min.kg). Neither Vo2 nor O2 extr changed significantly after dextran. No differences were noted in the response to dextran infusion comparing 5 to 14-day-old piglets with 3 to 5-wk-old piglets. Unlike fetal lambs, newborn piglets are able to elevate cardiac output significantly in response to volume loading. However, if these data can be extrapolated to human infants, volume infusion without concurrent blood transfusion is likely to increase systemic cardiac output but not improve Do2.


Erbium chloride silicate-based vertical cavity surface-emitting laser at the near-infrared communication band.
Silicon-based integrated optoelectronics has become a hotspot in the field of computers and information processing systems. An integrated coherent light source on-chip with a small footprint and high efficiency is one of the most important unresolved devices. Here, we realize a silicon-based vertical cavity surface-emitting laser in the near-infrared communication band by making efforts in both controlled preparation of high-gain erbium silicate materials and novel design of high optical feedback microcavity. Single-crystal erbium/ytterbium silicate microplates with erbium concentration as high as 5 × 1021 cm-3 are controlled prepared by a chemical vapor deposition method. They can produce strong luminescence with quite a long lifetime (2.3 ms) at the wavelength of 1.5 μm. By embedding the erbium silicate microplates between two dielectric Bragg reflectors, we construct a vertical cavity surface-emitting laser at 1.5 μm, with a lasing threshold as low as 20 μJ/cm2 and Q factor of nearly 2000. Our study provides a new pathway to achieve a sub-micrometer coherent light source for optical communication.


Glutathione depletion modulates methanol, formaldehyde and formate toxicity in cultured rat conceptuses.
The proposed use of methanol (H3COH) as an alternative to fossil fuels has prompted concern about potential health risks resulting from widespread environmental exposure. Methanol is teratogenic in rodents and, although the exact toxic species is not known, teratogenesis may result from the enzymatic biotransformation of H3COH to formaldehyde (CH2O) and formic acid causing increased biological reactivity and toxicity. A protective role for the antioxidant glutathione (GSH) has been described for H3COH, CH2O and formic acid toxicity in various biological systems but has yet to be evaluated in the developing conceptus. Whole embryo culture studies were conducted using GD 10-11 rat conceptuses to elucidate the relationship between H3COH and its metabolites and GSH status. Methanol exposure produced a decrease in normal growth parameters and a dose-dependent loss of viability. CH2O had deleterious effects on embryo growth and viability. Sodium formate (HCOONa) exposure resulted in a high mortality rate but viable embryos did not manifest any abnormalities. Methanol, CH2O, and HCOONa all produced a significant depletion of GSH in both embryo and VYS. Inhibition of GSH synthesis by L-buthionine-S,R-sulfoximine (BSO) treatment exacerbated H3COH, CH2O and HCOONa embryotoxicity. Interestingly, only H3COH/BSO and CH2O/BSO co-treatments caused increased malformation, while embryos treated with HCOONa/BSO did not produce any developmental deformities. These results implicate CH2O as the most embryotoxic H3COH metabolite, on a molar basis, in terms of causing dysmorphogenesis, alterations of normal growth parameters and embryolethality. HCOONa was selectively embryolethal and did not produce dysmorphogenesis. CH2O toxicity is potentiated by GSH depletion, indicating that GSH may be more directly involved in its detoxication in the embryo.


[Ambulatory monitoring of arterial hypertension].
Systemic high blood pressure is a very frequent disease. One characteristic is its daily continuous variability. Ambulatory monitoring of blood pressure has some advantages over the clinical blood pressure reading at the doctor's office. It is more precise, reliable, records the pressure at night and during sleep, avoids "white coat" phenomenon, among other things. This does not mean that blood pressure should not be taken during the regular medical visits. If there is any doubt of the presence of hypertension, blood pressure should be taken 3-4 times par day during several days to ensure the diagnosis, because one high blood pressure reading does not establish the diagnosis of systemic hypertension.


Ab initio molecular dynamics study of prebiotic production processes of organic compounds at meteorite impacts on ocean.
Recent experiments concerning prebiotic materials syntheses suggest that the iron-bearing meteorite impacts on ocean during Late Heavy Bombardment provided abundant organic compounds associated with biomolecules such as amino acids and nucleobases. However, the molecular mechanism of a series of chemical reactions to produce such compounds is not well understood. In this study, we simulate the shock compression state of a meteorite impact for a model system composed of CO2 , H2 O, and metallic iron slab by ab initio molecular dynamics combined with multiscale shock technique, and clarify possible elementary reaction processes up to production of organic compounds. The reactions included not only pathways similar to the Fischer-Tropsch process known as an important hydrocarbon synthesis in many planetary processes but also those resulting in production of a carboxylic acid. It is also found that bicarbonate ions formed from CO2 and H2 O participated in some forms in most of these observed elementary reaction processes. These findings would deepen the understanding of the full range of chemical reactions that could occur in the meteorite impact events. © 2018 Wiley Periodicals, Inc.


Oral health status and its association with nutritional support in malnourished patients hospitalised in acute care.
This cross-sectional study aimed to examine the oral health of malnourished acute-care hospital inpatients, who were the subjects of a nutritional support team (NST). We also aimed to elucidate the systemic and nutritional factors associated with the oral health of those patients. Interventions by NST are essential for inpatient nutrition management and require the active participation of dental professionals. However, information is limited regarding the state of oral health among acute-stage malnourished inpatients. We enrolled 255 hospitalised patients (101 women, mean age: 69.7 ± 14.4 years) who were referred to an NST for nutrition management between April 2016 and July 2019. The main outcome was the Oral Health Assessment Tool (OHAT) scores. Moreover, we assessed participants' demographic characteristics, nutritional status, number of natural and functional teeth, posterior occlusal support, denture use, Dysphagia Severity Scale, whether oral health management was needed, and the methods of nutrition intake. Several participants presented with a deteriorated oral health. Consequently, oral health management was often regarded necessary in these patients. Approximately half were fed by parenteral or tube feeding. Multiple regression analysis revealed the OHAT score has a positive association with age (P = .008), and a negative association with body mass index (P = .009) and the method of nutrition intake (P = .028). Malnourished inpatients at an acute care hospital who were subject to an NST had a deteriorated oral health status. Additionally, poor oral health was associated with poor nutritional status and nutrition intake methods.


ACTH initiation of mammary secretion in pregnant goats is influenced by the stage of gestation and pre partum milking.
Pregnant goats were treated with ACTH by intramuscular injection (1 mg/d for 2 d) at various stages of pregnancy to investigate its effect on initiation of mammary secretion. ACTH stimulated lactose secretion and increased udder volume at or after 84 d of gestation, when compared with untreated controls. Treatment with ACTH between d 109 and 127 of gestation increased circulating plasma glucose concentration, mammary blood flow and mammary uptake of glucose which returned to pre injection levels 6 d after treatment. Arterial concentrations of progesterone were not affected by ACTH but mammary progesterone uptake increased 2-fold. Pre partum milking alone stimulated mammary secretion in eight of 13 goats. Subsequent treatment with ACTH resulted in no further change in the composition of the secretion but increase in yield was maintained. ACTH stimulated mammary secretion in those goats which did not respond to pre partum milking. It was concluded that ACTH initiated mammary secretion in pregnant goats by mechanisms which interact with the stimulation of milking but which are independent of circulating progesterone levels.


Chemical peritonitis resulting from spontaneous rupture of a mature ovarian cystic teratoma: a case report.
Mature cystic teratomas (dermoid cysts) are the most common germ cell tumours with 10-25% incidence of adult and 50% of paediatric ovarian tumours. The aetiology of dermoid cysts is still unclear, although currently the parthenogenic theory is most widely accepted. The tumour is slow-growing and in the majority of cases it is an accidental finding. Presenting symptoms are vague and nonspecific. The main complication of a dermoid cyst is cyst torsion (15%); other reported complications include malignant transformation (1-2%), infection (1%), and rupture (0.3-2%). Prolonged pressure during pregnancy, torsion with infarction, or a direct trauma are the main risk factors for a spontaneous dermoid rupture that can lead to acute or chronic peritonitis. The diagnosis of mature cystic teratoma is often made in retrospect after surgical resection of an ovarian cyst, because such imaging modalities as ultrasound, computer tomography, or magnetic resonance imaging cannot yet accurately and reliably distinguish between benign and malignant pathology. We present a report of a clinical case of a 35-years-old female, who was referred to the hospital due to abdominal pain spreading to her feet for three successive days. She had a history of a normal vaginal delivery one month before. Abdominal examination revealed mild tenderness in the lower abdomen; no obvious muscle rigidity was noted. Transvaginal ultrasound showed a multiloculated cystic mass measuring 16 × 10 cm in the pelvis. In the absence of urgency, planned surgical treatment was recommended. The next day the patient was referred to the hospital again, with a complaint of stronger abdominal pain (7/10), nausea, and vomiting. This time abdominal examination revealed symptoms of acute peritonitis. The ultrasound scan differed from the previous one. This time, the transvaginal ultrasound scan revealed abnormally changed ovaries bilaterally. There was a large amount of free fluid in the abdominal cavity. The patient was operated on - left laparoscopic cystectomy and right adnexectomy were performed. Postoperative antibacterial treatment, infusion of fluids, painkillers, prophylaxis of the thromboembolism were administered. The patient was discharged from the hospital on the seventh postoperative day and was sent for outpatient observation. Ultrasound is the imaging modality of choice for a dermoid cyst because it is safe, non-invasive, and quick to perform. Leakage or spillage of dermoid cyst contents can cause chemical peritonitis, which is an aseptic inflammatory peritoneal reaction. Once a rupture of an ovarian cystic teratoma is diagnosed, immediate surgical intervention with prompt removal of the spontaneously ruptured ovarian cyst and thorough peritoneal lavage are required.


Differences in Epstein-Barr virus expression between primary and secondary cutaneous angiocentric lymphomas. French Study Group of Cutaneous Lymphomas.
Epstein-Barr virus (EBV) has been demonstrated in angiocentric immunoproliferative lesions, suggesting that it could be a causative factor. We investigated for the presence of EBV in 12 primary and 2 secondary cutaneous angiocentric lymphomas (CALs). In the 2 secondary CALs, strong reactivity for EBV RNAs and latent membrane protein 1 were detected on paraffin-embedded sections. In contrast, 10 of 12 primary CALs were completely negative for EBV RNAs and latent membrane protein 1. In 2 primary CALs, EBV RNAs and latent membrane protein 1 were detected in few tumor cells. In the group of primary CALs, 8 of 12 were still alive at last follow-up, 3 died of systemic lymphoma, and 1 died of another cause, whereas both patients with secondary CALs died of disease within 1 year. Differences in the presence of EBV and clinical behavior between primary and secondary CALs suggest that different mechanisms are operative in the pathogenesis of these conditions, and indicate that the 2 groups should be considered separately.


Trust in managed care organizations.
Two basic criticisms of managed care are that it erodes patient trust in physicians and subjects physicians to incentives and pressures that compromise the physician's fiduciary obligation to the patient. In this article, I first distinguish between status trust and merit trust, and then argue (1) that the value of status trust in physicians is probably over-rated and certainly underdocumented; (2) that erosion of status trust may not be detrimental if accompanied by an increase in well-founded merit trust; and (3) that under conditions of managed care the physician's commitment to traditional medical ethics cannot serve as an adequate basis for merit trust. Next, drawing on an analogy between managed care organzations and politics, I argue that (4) the most appropriate basis for merit trust in managed care is a conception of organizational legitimacy that includes procedural justice, empowerment of constructive criticism within the organization, and organizational accommodation of the noninstrumental commitment to patient well-being that is distinctive of medical professionalism. I then explore the conditions necessary for robust competition for merit trust among managed care organizations and indicate the kinds of public policies needed to facilitate such competition. Finally, I show how the account of organization-based merit trust can accommodate the special fiduciary obligation of medical professionals, without indulging in the delusion that it is the physician's fiduciary obligation always to provide all care that is expected to be of any net benefit to the patient.


Developing and proposing the ethno-cultural gerontological nursing model.
By 2050, for the first time in U.S. history, almost half of elders will be from ethnic minority groups. To meet the needs of this rapidly diversifying population, nurses need to be able to marry transcultural nursing knowledge with gerontological nursing knowledge. The purpose of this article is to propose a new theoretical model for explaining health outcomes and health responses for older individuals in unique ethno-cultural groups and to discuss implications and applications of the model to transcultural gerontological nursing practice and research. The discussion will include (1) an overview of currently available theoretical knowledge in the area, (2) a description of the theory development process, (3) presentation of the proposed ethno-cultural gerontological nursing theoretical model, and (4) discussion of how this model can enhance nursing's contributions to reducing health disparities. This model is presented not as a finished product but as a basis for future discussion and refinement.


Auditory filters and the benefit measured from spectral enhancement.
Algorithms designed to improve speech intelligibility for those with sensorineural hearing loss (SNHL) by enhancing peaks in a spectrum have had limited success. Since testing of such algorithms cannot separate the theory of the design from the implementation itself, the contribution of each of these potentially limiting factors is not clear. Therefore, psychophysical paradigms were used to test subjects with either normal hearing or SNHL in detection tasks using well controlled stimuli to predict and assess the limits in performance gain from a spectrally enhancing algorithm. A group of normal-hearing (NH) and hearing-impaired (HI) subjects listened in two experiments: auditory filter measurements and detection of incremented harmonics in a harmonic spectrum. The results show that NH and HI subjects have an improved ability to detect incremented harmonics when there are spectral decrements surrounding the increment. Various decrement widths and depths were compared against subjects' equivalent rectangular bandwidths (ERBs). NH subjects effectively used the available energy cue in their auditory filters. Some HI subjects, while showing significant improvements, underutilized the energy reduction in their auditory filters.


Glutathione-glutaredoxin is an efficient electron donor system for mammalian p53R2-R1-dependent ribonucleotide reductase.
Deoxyribonucleotides are DNA building blocks and are produced de novo by reduction of ribose to deoxyribose. This reduction is catalyzed by ribonucleotide reductase (RNR), a heterodimeric tetramer enzyme in mammalian cells, having one of two free radical-containing subunits called R2 and p53R2. R2 is S-phase specific and used for DNA replication, whereas p53R2 functions in DNA repair and mitochondrial DNA synthesis. The larger RNR subunit, R1, has catalytically active cysteine thiols in its buried active site and a C-terminal swinging arm, with a Cys-Leu-Met-Cys sequence suggested to act as a shuttle dithiol/disulfide for electron transport. After each catalytic cycle the active site contains a disulfide, which has to be reduced for turnover. Thioredoxin (Trx) and glutaredoxin (Grx) systems have been implicated as electron donors for the RNR disulfide reduction via the swinging arm. Using mouse R1-R2 and R1-p53R2 complexes, we found here that the catalytic efficiency of the GSH-Grx system is 4-6 times higher than that of the Trx1 system. For both complexes, the Vmax values for Grx are strongly depended on GSH concentrations. The GSH disulfide resulting from the Grx reaction was reduced by NADPH and GSH reductase and this enzyme was essential because reaction with GSH alone yielded only little activity. These results indicate that C-terminal shuttle dithiols of mammalian R1 have a crucial catalytic role and that the GSH-Grx system favors the R1-p53R2 enzyme for DNA replication in hypoxic conditions, mitochondrial DNA synthesis, and in DNA repair outside the S-phase.