Validation of the ^{10}Be Ground-State Molecular Structure Using ^{10}Be(p,pα)^{6}He Triple Differential Reaction Cross-Section Measurements.
The cluster structure of the neutron-rich isotope ^{10}Be has been probed via the (p,pα) reaction at 150 MeV/nucleon in inverse kinematics and in quasifree conditions. The populated states of ^{6}He residues were investigated through missing mass spectroscopy. The triple differential cross section for the ground-state transition was extracted for quasifree angle pairs (θ_{p},θ_{α}) and compared to distorted-wave impulse approximation reaction calculations performed in a microscopic framework using successively the Tohsaki-Horiuchi-Schuck-Röpke product wave function and the wave function deduced from antisymmetrized molecular dynamics calculations. The remarkable agreement between calculated and measured cross sections in both shape and magnitude validates the molecular structure description of the ^{10}Be ground-state, configured as an α-α core with two valence neutrons occupying π-type molecular orbitals.


[Nocturnal enuresis as a manifestation of autocoidosis].
The study entered 30 children with nocturnal enuresis and 20 healthy controls aged 6-15 years. The enuretic children had a higher night diuresis and free water reabsorption; there was an increase in nocturnal excretion of sodium, calcium and magnesium ions. Before going to bed the patients received diclofenac-sodium. Inhibition of cyclooxygenase and decrease of prostaglandin production led to normalization of diuresis and natriuresis, elimination of nocturnal enuresis episodes. The evidence has been obtained that nocturnal enuresis is accompanied by an increased production of autocoids in the thick ascending Henle loop and, as a result, of an increase in saluresis and diuresis. It is suggested that there is a form of nocturnal diuresis which depends on a local hyperproduction of autocoids. The problem of autocoids role in the internal medicine is discussed.


Exposure of hairdressing apprentices to airborne hazardous substances.
Few studies have investigated exposure of hairdressing apprentices to airborne irritants. This study describes exposure levels of apprentices to chemical products used in hairdressing salons in relation with their activity. Following a two stages study design, a group of 300 students completed a questionnaire on their work activities and environment. Among these, a group of 28 subjects volunteered to undergo personal exposure and workplace concentrations measurements over a work shift, during a cold and a hot season, with the agreement of the salon owners. Three chemical substances were studied (ammonia, hydrogen peroxide and persulfates) because they are respiratory tract irritants and because their concentrations could be quantified within a 5 to 8 hour shift period. Personal exposure values for H2O2 and NH3 (averages [standard deviations] are 0.05 [0.04] and 0.90 [0.76] mg.m(-3), respectively) were greater than workplace ambient air concentrations (corresponding values of 0.04 [0.03] and 0.68 [0.42] mg.m(-3)) for H2O2 and NH3, with no significant seasonal variation. By contrast, workplace concentrations of persulfates (0.019 [0.018] mg.m(-3)) were greater than personal exposure (0.016 [0.021] mg.m(-3), a finding that is consistent with the fact that bleaching is more often undertaken by senior hairdressers. However, all exposure values were lower than the current TLV TWA values. This study also shows that over half of technical spaces where chemical substances used for dying, permanenting or bleaching are manipulated, have no ventilation system, and not even a door or a window opening outside. The study hairdressing salons, on average, were small, the most probable reason why occupational hygiene measures such as appropriate ventilation were too seldom implemented. As a consequence, young apprentices and senior hairdressers experience substantial exposure to known airways irritants.


The 3'-->5' exonuclease of DNA polymerase delta can substitute for the 5' flap endonuclease Rad27/Fen1 in processing Okazaki fragments and preventing genome instability.
Many DNA polymerases (Pol) have an intrinsic 3'-->5' exonuclease (Exo) activity which corrects polymerase errors and prevents mutations. We describe a role of the 3'-->5' Exo of Pol delta as a supplement or backup for the Rad27/Fen1 5' flap endonuclease. A yeast rad27 null allele was lethal in combination with Pol delta mutations in Exo I, Exo II, and Exo III motifs that inactivate its exonuclease, but it was viable with mutations in other parts of Pol delta. The rad27-p allele, which has little phenotypic effect by itself, was also lethal in combination with mutations in the Pol delta Exo I and Exo II motifs. However, rad27-p Pol delta Exo III double mutants were viable. They exhibited strong synergistic increases in CAN1 duplication mutations, intrachromosomal and interchromosomal recombination, and required the wild-type double-strand break repair genes RAD50, RAD51, and RAD52 for viability. Observed effects were similar to those of the rad27-null mutant deficient in the removal of 5' flaps in the lagging strand. These results suggest that the 3'-->5' Exo activity of Pol delta is redundant with Rad27/Fen1 for creating ligatable nicks between adjacent Okazaki fragments, possibly by reducing the amount of strand-displacement in the lagging strand.


Identification of QTL for barley grain size.
Barley grain size is one of the key factors determining storage capacity during grain filling. Large, well-filled grains also have a high malt extract potential. Grain size is a complex quantitative trait and can be easily affected by environmental factors thus the identification of genes controlling the trait and the use of molecular markers linked to the genes in breeding program is the most effective way of improving grain size. Grain sizes of 188 doubled-haploid (DH) lines derived from the cross of a Japanese malting barley variety (Naso Nijo) and a Chinese feed barley variety (TX9425) were obtained from three different sites in two consecutive years. The average data were used for identifying QTL for grain size. A total of four significant QTL were identified for grain length (GL) and three for grain width (GW). The two major GL QTL are located at similar positions to the QTL for malt extract on 2H and uzu gene on 3H, respectively. However, the GL QTL on 2H is more likely a different one from the malt extract QTL as most of the candidate genes are located outside the fine mapped QTL region for malt extract. The GL QTL on 3H is closely linked with uzu gene but not due to a pleiotropic effect of uzu. The three QTL for grain width on 1H, 2H and 5H, respectively, were located at same position to those for GL.


[DNA repair system in nonspecific lung diseases].
It has been found that in 35-40% of patients with acute and chronic pneumonia, the reduced ability of peripheral blood lymphocytes for DNA repair is encountered 14 times as frequently as in normal subjects. After discontinuation of antibacterial therapy with penicillin or tetracycline antibiotics marked inhibition of the ability of lymphocytes for DNA repair is recorded. The tendency toward normalization of this characteristic occurs 1 week after discontinuation of antibiotic therapy for acute and 3 weeks for chronic pneumonia. The disorders of the ability of peripheral blood lymphocytes for DNA repair in the conditions under study are regarded as a possible cause of secondary immunodeficiency.


Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease.
Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.


Collagen vitrigels with low-fibril density enhance human embryonic stem cell-derived retinal pigment epithelial cell maturation.
Structural and biochemical cues of extracellular matrix can substantially influence the differentiation and maturation of cultured retinal pigment epithelial (RPE) cells. In this study, thin collagen vitrigels were engineered to create collagen nanofibrillar structures of different fibril densities in an effort to evaluate the maturation of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells. The ultrastructure of the different collagen vitrigels was characterized by transmission electron microscopy, and the mechanical properties were evaluated by tensile testing. The pigmentation and polarization of cells, in addition to key RPE marker gene and protein expression levels, were analyzed to determine the differentiation of hESCs on the gels. The hESC-RPE differentiation was most significant in collagen vitrigels with low fibril density with mature collagen fibrils with diameter of around 60 nm and Young's modulus of 2.41 ± 0.13 MPa. This study provides insight into the influence of collagen nanofibrillar structures on hESC-RPE maturation and presents a potential bioengineered substratum for hESC-RPE for future preclinical and clinical applications.


Pentoxifylline and vitamin E treatment for prevention of radiation-induced side-effects in women with breast cancer: a phase two, double-blind, placebo-controlled randomised clinical trial (Ptx-5).
A previous study has shown that pentoxifylline in combination with vitamin E can reverse radiation-induced fibrosis. The aim of the present study is to investigate if the same drugs could prevent radiation-induced side-effects in women with breast cancer. A randomised, placebo-controlled, double-blind, parallel group trial was performed. Women with breast cancer were treated for 12 months with 400 mg pentoxifylline t.i.d. or placebo, in combination with 100 mg vitamin E t.i.d., starting 1-3 months after the completion of radiotherapy. The primary end-point was passive abduction of the shoulder, and the secondary end-point was difference in arm volumes. The trial is registered on the ISRCTN.org website, number ISRCTN39143623. 83 patients were included in the study; 42 in the pentoxifylline+vitamin E group and 41 in the placebo+vitamin E group. Both treatments were generally well tolerated. Seven patients were withdrawn from the treatment due to disease progression; four in the pentoxifylline group and three in the placebo group. At inclusion, patients had impaired passive abduction of the shoulder. During treatment, both the groups improved significantly. Median improvement from baseline was 3.7 degrees (p=0.0035) on pentoxifylline and was 9.4 degrees (p=0.0041) in the placebo group, but no difference between the groups was detected (p=0.20). Arm volumes increased over time in the placebo group (1.04%), but not on pentoxifylline (0.50%), and differed significantly between the groups (p=0.0172). The combination of pentoxifylline and vitamin E was safe and may be used for the prevention of some radiation-induced side-effects.


Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: a literature review and potential mechanisms of action.
Numerous reports of the induction or worsening of psoriasis in patients treated with tumor necrosis factor (TNF) antagonists indicate that this is not a rare phenomenon. The etiology of this paradoxical clinical response remains unclear. The aim of this study was to describe similar cases, conduct a comprehensive analysis of the literature, explore possible immunologic mechanisms of action of this perplexing reaction, and recommend management options. A systematic literature review was performed using the PubMed and Medline databases (1996 to September 2007) searching the index terms "infliximab," "etanercept," "adalimumab," "tumor necrosis factor alpha inhibitor," and "TNF inhibitor," combined with the terms "psoriasis," "pustular," "skin," "rash," and "palmoplantar." All relevant articles in English were reviewed. Pertinent secondary references were also analyzed. According to the literature, new-onset psoriasis may occur any time after initiation of TNF antagonist therapy, is often of an uncommon morphology, may respond to psoriasis treatments, and usually resolves with TNF discontinuation. The pathogenesis of this response appears to involve a disruption in cytokine balance following TNF inhibition, resulting in the up-regulation of plasmacytoid dendritic cells and the subsequent production of unopposed interferon-alpha, following a triggering event in predisposed individuals. TNF antagonist-induced psoriasis is a newly recognized adverse effect of these medications that typically does not require therapy cessation. We recommend aggressive treatment of the skin disease and consideration of a change in the TNF antagonist if the lesions are unresponsive to conventional psoriasis treatment.


Drug-eluting stent: a review and update.
The development of stent has been a major advance in the treatment of obstructive coronary artery disease since the introduction of balloon angioplasty. However, neointimal hyperplasia occurring within the stent leading to in-stent restenosis is a main obstacle in the long-term success of percutaneous coronary intervention (PCI). The recent introduction of drug-eluting stents (DES) contributes a major breakthrough to interventional cardiology. Many large randomized clinical trials using DES have shown a remarkable reduction in angiographic restenosis and target vessel revascularization when compared with bare metal stents. The results of these trials also appear to be supported by evidence from everyday practice and non-controlled clinical trials. However, the expanded applications of DES, especially in treating complex lesions such as left main trunk, bifurcation, saphenous vein graft lesions, or in-stent restenosis, are still under evaluation with ongoing studies. With the availability of different types of DES in the market, the issue of cost should not be a deterrent and DES will eventually be an economically viable option for all patients. The adoption of DES in all percutaneous coronary intervention may become a reality in the near future. In this review article, we summarize the recent development and progress of DES as well as compare and update the results of clinical trials.


Neonatal platelets: mediators of primary hemostasis in the developing hemostatic system.
The human hemostatic system is developmentally regulated, resulting in qualitative and quantitative differences in the mediators of primary and secondary hemostasis as well as fibrinolysis in neonates and infants. Although gestational age-related differences in coagulation factor levels occur, the existence of a unique neonatal platelet phenotype remains controversial. Complicated by difficulties in obtaining adequate neonatal blood volumes with which to perform functional assays, ambiguity surrounds the characterization of neonatal platelets. Thus, much of the current knowledge of neonatal platelet function has been based on studies from cord blood samples. Studies suggest that cord blood-derived platelets, as a surrogate for neonatal platelets, are hypofunctional when compared with adult platelets. This relative platelet dysfunction, combined with a propensity toward thrombocytopenia in the neonatal intensive care unit population, creates a clinical conundrum regarding the appropriate administration of platelet transfusions. This review provides an appraisal of the distinct functional phenotype of neonatal platelets. Neonatal platelet transfusion practices and the impact of the relatively hypofunctional neonatal platelet on those practices will be considered.


The T Cell Receptor Immune Repertoire Protects the Liver From Reconsitution.
Aberrant immune cell infiltrates and microcircumstances represent characteristic features of liver fibrosis. In this study, we profiled the transcriptomes of intrahepatic CD45+ immune cells, from mice, using single-cell RNA sequencing (scRNA-seq) technology to understand the landscape of intrahepatic immune cells during the pathogenesis of fibrosis. Analysis of approximately 10,000 single-cell transcriptomes revealed an increase in dendritic cells (DCs), macrophages, and neutrophils and a decrease in T and natural killer T (NKT) cells. In addition, we report changes in the transcriptomes of diverse immune cell types, implying a deteriorating intrahepatic immune microcircumstance. Furthermore, we uncovered a novel fibrosis-associated CD8 T (Ccl5+, Ccl4+) and CD4 T (mt-Co1+) cell subpopulation, which infiltrates fibrotic liver and is characterized by abnormal activation or inactivation as well as a TCR decline. The results from scRNA-seq and bulk immune repertoire sequencing (IR-seq) revealed an obvious decline in T cell receptor (TCR) clonotypes combined with shrinking VJ and VDJ segment usage, as well as lower complementarity-determining region 3 (CDR3) amino acid (AA) diversity from fibrotic liver. Interestingly, a deficiency of TCR IR (TcrbKO mice) led to a deterioration of liver fibrosis, coupled with activation of hepatic stellate cells (HSCs) induced by the upregulation of macrophage and γδ T cell distribution in fibrotic TcrbKO livers. Our findings reveal the landscape and dynamics of single immune cells in liver fibrosis, and clarify the protective role of TCR IR in response to chronic liver injury.


Electricity usage scheduling in smart building environments using smart devices.
With the recent advances in smart grid technologies as well as the increasing dissemination of smart meters, the electricity usage of every moment can be detected in modern smart building environments. Thus, the utility company adopts different price of electricity at each time slot considering the peak time. This paper presents a new electricity usage scheduling algorithm for smart buildings that adopts real-time pricing of electricity. The proposed algorithm detects the change of electricity prices by making use of a smart device and changes the power mode of each electric device dynamically. Specifically, we formulate the electricity usage scheduling problem as a real-time task scheduling problem and show that it is a complex search problem that has an exponential time complexity. An efficient heuristic based on genetic algorithms is performed on a smart device to cut down the huge searching space and find a reasonable schedule within a feasible time budget. Experimental results with various building conditions show that the proposed algorithm reduces the electricity charge of a smart building by 25.6% on average and up to 33.4%.


A new treatment for frostbite sequelae; Botulinum toxin.
Frostbite sequelae are a relevant occupational injury outcome for soldiers in arctic environments. A Caucasian male soldier suffered frostbite to both hands during a military winter exercise. He developed sensory-motor disturbances and cold hypersensitivity. Angiography and thermography revealed impaired blood flow while Quantitative Sensory Testing indicated impaired somato-sensory nerve function. Two years after the initial event, he received an off label treatment with Botulinum toxin distributed around the neurovascular bundles of each finger. After treatment, cold sensitivity was reduced while blood flow and somato-sensory nerve function improved. The successful treatment enabled the soldier to successfully pursue his career in the army.


Dietary supplementation by older adults in Japan.
This study documented the prevalence and pattern of dietary supplements usage among older adults in Japan. Persons aged 55-75 years residing in middle and southern Japan were recruited and interviewed face-to-face on their use of dietary supplements. Among the 572 (355 male and 217 female) participants from 10 prefectures, 45.8% took supplements on a weekly or daily basis, the prevalence was higher for women (52.5%) than men (41.7%). Many types of miscellaneous supplements were consumed. The most popular supplement was vinegar for both men (11.0%) and women (15.2%), followed by energy drink (8.5%) for men, and multivitamin (8.5%) for men and vitamin C (8.3%) for women. The findings suggested an increasing trend of dietary supplementation by Japanese older adults when compared to previous studies.


Functional coupling of transcription factor HiNF-P and histone H4 gene expression during pre- and post-natal mouse development.
Transcription factor Histone Nuclear Factor P (HiNF-P; gene symbol Hinfp) mediates cell cycle control of histone H4 gene expression to support the packaging of newly replicated DNA as chromatin. The HiNF-P/p220(NPAT) complex controls multiple H4 genes in established human cell lines and is critical for cell proliferation. The mouse Hinfp(LacZ) null allele causes early embryonic lethality due to a blastocyst defect. However, neither Hinfp function nor its temporal expression relative to histone H4 genes during fetal development has been explored. Here, we establish that expression of Hinfp is biologically coupled with expression of twelve functional mouse H4 genes during pre- and post-natal tissue-development. Both Hinfp and H4 genes are robustly expressed at multiple embryonic (E) days (from E5.5 to E15.5), coincident with ubiquitous LacZ staining driven by the Hinfp promoter. Five highly expressed mouse H4 genes (Hist1h4d, Histh4f, Hist1h4m and Hist2h4) account for >90% of total histone H4 mRNA throughout development. Post-natal expression of H4 genes in mice is most evident in lung, spleen, thymus and intestine, and with few exceptions (e.g., adult liver) correlates with Hinfp gene expression. Histone H4 gene expression decreases butHinfp levels remain constitutive upon cell growth inhibition in culture. The in vivo co-expression of Hinfp and histone H4 genes is consistent with the biological function of Hinfp as a principal transcriptional regulator of histone H4 gene expression during mouse development.


Next-generation serology: integrating cross-sectional and capture-recapture approaches to infer disease dynamics.
Two approaches have been classically used in disease ecology to estimate epidemiological parameters from field studies: cross-sectional sampling from unmarked individuals and longitudinal capture-recapture setups, which generally involve more limited numbers of marked individuals due to cost and logistical constraints. Although the benefits of longitudinal setups are increasingly acknowledged in the disease ecology community, cross-sectional data remain largely overrepresented in the literature, probably because of the inherent costs of longitudinal surveys. In this context, we used simulated data to compare the performances of cross-sectional and longitudinal designs to estimate the force of infection (i.e., the rate at which susceptible individuals become infected). Then, inspired from recent method developments in quantitative ecology, we explore the benefits of integrating both cross-sectional (seroprevalences) and longitudinal (individuals histories) data sets. In doing so, we investigate the effects of host species life history, antibody persistence, and degree of a priori knowledge and uncertainty on demographic and epidemiological parameters, as those are expected to affect in different ways the level of inference possible from the data. Our results highlight how those elements are important to consider in determining optimal sampling designs. In the case of long-lived species exposed to infectious agents resulting in persistent antibody responses, integrated designs are especially valuable as they benefit from the performances of longitudinal designs even with relatively small longitudinal sample sizes. As an illustration, we apply this approach to a combination of empirical and simulated data inspired from a case of bats exposed to a rabies virus. Overall, this work highlights that serology field studies could greatly benefit from the opportunity of integrating cross-sectional and longitudinal designs.


Patch-Based Discrete Registration of Clinical Brain Images.
We introduce a method for registration of brain images acquired in clinical settings. The algorithm relies on three-dimensional patches in a discrete registration framework to estimate correspondences. Clinical images present significant challenges for computational analysis. Fast acquisition often results in images with sparse slices, severe artifacts, and variable fields of view. Yet, large clinical datasets hold a wealth of clinically relevant information. Despite significant progress in image registration, most algorithms make strong assumptions about the continuity of image data, failing when presented with clinical images that violate these assumptions. In this paper, we demonstrate a non-rigid registration method for aligning such images. The method explicitly models the sparsely available image information to achieve robust registration. We demonstrate the algorithm on clinical images of stroke patients. The proposed method outperforms state of the art registration algorithms and avoids catastrophic failures often caused by these images. We provide a freely available open source implementation of the algorithm.


Effects of polycyclic aromatic hydrocarbons in northern bobwhite quail (Colinus virginianus).
Polycyclic aromatic hydrocarbons (PAH) are ubiquitous contaminants of aquatic and terrestrial ecosystems, and are known to induce biochemical alterations in exposed organisms. Aside from a variety of adverse physiological effects associated with exposure to petroleum products, oils, and oil sludges, little is known about the effects of individual PAH on birds. Acute toxicity of naphthalene, pyrene, and benz[a]anthracene (BAA) was examined in adult northern bobwhite quail (Colinus virginianus). Additionally, subacute (8 d) and subchronic (60 d) studies were conducted to assess alterations in metabolic enzyme activity. Neither naphthalene, nor pyrene, nor BAA exposure via oral gavage produced acute toxicity up to the limit dose of 2 g/kg body weight. In the subacute study, quail provided feed containing the highest concentration of BAA for 5 d had significantly increased renal ethoxyresorufin O-deeththylase (EROD) activity compared to controls. Following a 3-d recovery period, significant increases between 10 and 100 mg/kg of BAA in feed existed for both hepatic EROD and pentoxyresorufin O-deethylase (PROD) activity compared to controls. Subchronic exposure to BAA (ranging from 0.1 to 10 mg/kg) also resulted in a significant rise of EROD and PROD in both kidney and liver tissue compared to controls. Though the individual PAH used in this study were not acutely toxic, these results confirm that these individual PAH induce alterations in metabolic enzyme activity in northern bobwhite quail.


Unique apicomplexan IMC sub-compartment proteins are early markers for apical polarity in the malaria parasite.
The phylum Apicomplexa comprises over 5000 intracellular protozoan parasites, including Plasmodium and Toxoplasma, that are clinically important pathogens affecting humans and livestock. Malaria parasites belonging to the genus Plasmodium possess a pellicle comprised of a plasmalemma and inner membrane complex (IMC), which is implicated in parasite motility and invasion. Using live cell imaging and reverse genetics in the rodent malaria model P. berghei, we localise two unique IMC sub-compartment proteins (ISPs) and examine their role in defining apical polarity during zygote (ookinete) development. We show that these proteins localise to the anterior apical end of the parasite where IMC organisation is initiated, and are expressed at all developmental stages, especially those that are invasive. Both ISP proteins are N-myristoylated, phosphorylated and membrane-bound. Gene disruption studies suggest that ISP1 is likely essential for parasite development, whereas ISP3 is not. However, an absence of ISP3 alters the apical localisation of ISP1 in all invasive stages including ookinetes and sporozoites, suggesting a coordinated function for these proteins in the organisation of apical polarity in the parasite.


Frequency of extra pulmonary complications in critically ill COVID-19 patients and their association with inflammatory markers and hypoxia: Retrospective analysis at a tertiary care hospital in Karachi, Pakistan.
This study aimed to determine the incidence of extra pulmonary complications among critically ill COVID-19 patients requiring invasive mechanical ventilation and association of these complications with various inflammatory markers and degree of hypoxia. A retrospective cohort study was conducted among 173 adults in Karachi having COVID-19 and were admitted to ICU in a tertiary care private hospital between August 2020 to July 2021. The median age of patients included in the analysis was 61 years (IQR; 16). Acute kidney injury, septic shock, cardiac injury, and electrolytes imbalance were the most frequent extra pulmonary complications with proportion of 65.3% (n=113), 63.6% (n=110), 61.8% (n=107) and 33.5% (n=58). Statistically significant differences in the median serum levels of ferritin were observed among male versus female, critically ill covid patients with and without ICU mortality as well as patients with and without hospital mortality (p-value <0.05). Significantly higher serum levels of d-dimer were noted among patients who developed acute liver injury or NSTEMI, or had ICU stay of > 3 days or received mechanical ventilation for >2 days. Acute kidney injury, septic shock, cardiac injury, and electrolytes imbalance were the most common extra pulmonary complications among mechanically ventilated COVID-19 patients with ARDS. Higher serum d-dimer levels were associated with acute liver injury, NSTEMI, ICU stay longer >3 days and invasive mechanical ventilation >2 days. Higher serum ferritin levels are associated with male sex and serve as an important predictor of ICU as well as hospital mortality.


[The Capgras syndrome].
A new case of Capgras' syndrome is presented with a short review on the subject. Since there are many controversies about the etiology of this syndrome, and since some authors explain it with organic factors, others with psychodynamic factors, or a combination of the two, one should be careful with this syndrome to eliminate the presence of organic factors with a meticulous physical examination and appropriate neuropsychological tests. A thorough examination of early interpersonal relations is necessary to verify psychodynamic hypothesis, the most plausible being the splitting of internalized object representations.


The use of a generalized reconstruction by inversion of coupled systems (GRICS) approach for generic respiratory motion correction in PET/MR imaging.
Respiratory motion is a source of artifacts in multimodality imaging such as PET/MR. Solutions include retrospective or prospective gating. They have however found limited use in clinical practice, since their increased overall acquisition duration to maintain overall image quality. More elaborate methods consist of using 4D MR datasets to extract spatial deformations in order to correct for the respiratory motion in PET. The main drawbacks of such approaches is the relatively long acquisition times associated with 4D MR imaging which is often incompatible with clinical PET/MR protocols. The objective of this work was to overcome these limitations by exploiting a generalized reconstruction by inversion of coupled systems (GRICS) approach. The methodology is based on a joint estimation of motion during the MR image reconstruction process, providing internal structure motion and associated deformation matrices for retrospective use in PET respiratory motion correction. This method was first validated on four MR volunteers and two PET/MR patient datasets by comparing GRICS generated MR images to 4D MR series obtained by retrospective gating. In a second step 4D PET datasets corresponding to acquired 4D MR images were simulated using the GATE Monte Carlo simulation platform. GRICS generated deformation matrices were subsequently used to correct respiratory motion in comparison to the 4D MR image based deformations both for the simulated and the two 4D PET/MR patient datasets. Results confirm that GRICS synchronized MR images correlate well with the acquired 4D MR series. Similarly, the use of GRICS for respiratory motion correction allows an equivalent percentage improvement on lesion contrast, position and size, considering the PET simulated tumors as well as PET real tumors. This work demonstrates the potential interest of using GRICS for PET respiratory motion correction in combined PET/MR using shorter duration acquisitions without the need for 4D MRI and associated specific MR sequences.


Beyond spinal manipulation: should Medicare expand coverage for chiropractic services? A review and commentary on the challenges for policy makers.
Private insurance plans typically reimburse doctors of chiropractic for a range of clinical services, but Medicare reimbursements are restricted to spinal manipulation procedures. Medicare pays for evaluations performed by medical and osteopathic physicians, nurse practitioners, physician assistants, podiatrists, physical therapists, and occupational therapists; however, it does not reimburse the same services provided by chiropractic physicians. Advocates for expanded coverage of chiropractic services under Medicare cite clinical effectiveness and patient satisfaction, whereas critics point to unnecessary services, inadequate clinical documentation, and projected cost increases. To further inform this debate, the purpose of this commentary is to address the following questions: (1) What are the barriers to expand coverage for chiropractic services? (2) What could potentially be done to address these issues? (3) Is there a rationale for Centers for Medicare and Medicaid Services to expand coverage for chiropractic services? A literature search was conducted of Google and PubMed for peer-reviewed articles and US government reports relevant to the provision of chiropractic care under Medicare. We reviewed relevant articles and reports to identify key issues concerning the expansion of coverage for chiropractic under Medicare, including identification of barriers and rationale for expanded coverage. The literature search yielded 29 peer-reviewed articles and 7 federal government reports. Our review of these documents revealed 3 key barriers to full coverage of chiropractic services under Medicare: inadequate documentation of chiropractic claims, possible provision of unnecessary preventive care services, and the uncertain costs of expanded coverage. Our recommendations to address these barriers include the following: individual chiropractic physicians, as well as state and national chiropractic organizations, should continue to strengthen efforts to improve claims and documentation practices; and additional rigorous efficacy/effectiveness research and clinical studies for chiropractic services need to be performed. Research of chiropractic services should target the triple aim of high-quality care, affordability, and improved health. The barriers that were identified in this study can be addressed. To overcome these barriers, the chiropractic profession and individual physicians must assume responsibility for correcting deficiencies in compliance and documentation; further research needs to be done to evaluate chiropractic services; and effectiveness of extended episodes of preventive chiropractic care should be rigorously evaluated. Centers for Medicare and Medicaid Services policies related to chiropractic reimbursement should be reexamined using the same standards applicable to other health care providers. The integration of chiropractic physicians as fully engaged Medicare providers has the potential to enhance the capacity of the Medicare workforce to care for the growing population. We recommend that Medicare policy makers consider limited expansion of Medicare coverage to include, at a minimum, reimbursement for evaluation and management services by chiropractic physicians.


Pancreatic regeneration after partial pancreatectomy.
The ability of the pancreas to regenerate and the effects of trophic hormones on regeneration of the pancreas after partial pancreatectomy are not completely understood. We investigated the effects of the trypsin inhibitor FOY-305 (an agent that stimulates endogenous cholecystokinin) on pancreatic regeneration after partial pancreatectomy in rats. FOY-305 or water was administered for either 13 days or 27 days by gavage feeding, after sham operation or partial pancreatectomy (n = 6 to 8 animals per group). FOY-305 stimulated hypertrophy of the pancreatic remnant at 13 days; prolonged treatment for 27 days produced both hypertrophy and hyperplasia. The magnitude of pancreatic growth after FOY-305 administration was significantly greater at 27 days in the pancreatic remnant than growth of the equivalent pancreatic segment (duodenal and parabiliary) in sham-operated rats treated with FOY-305. Our results suggest that endogenous cholecystokinin released by FOY-305 stimulates regeneration after partial pancreatectomy. The pancreatic remnant is more sensitive to trophic stimulation in comparison to the normal pancreas. FOY-305 may be a useful agent in the treatment of pancreatic insufficiency after extensive subtotal pancreatectomy or chronic pancreatitis.


A case of keratitis associated with limbal relaxing incision.
We report a case of keratitis associated with limbal relaxing incision (LRI). The patient presented with progressive loss of vision with best-corrected visual acuity 20/40. Immature cataract with 1.43D against the rule astigmatism was noted. Prophylactic topical antibiotic was administered before surgery. He underwent uneventful phacoemulsification with intraocular lens implantation with LRI. On the 33rd postoperative day (POD), he presented with infiltrate along LRI site with mild iritis. Corneal scraping was positive for Staphylococcus aureus. After the treatment with topical moxifloxacin and fortified cefazolin, the infiltrate started to resolve. On the 50th POD, the corneal infection was resolved with marked thinning at LRI site.


In silico analyses suggest the cardiac ganglion of the lobster, Homarus americanus, contains a diverse array of putative innexin/innexin-like proteins, including both known and novel members of this protein family.
Gap junctions are physical channels that connect adjacent cells, permitting the flow of small molecules/ions between the cytoplasms of the coupled units. Innexin/innexin-like proteins are responsible for the formation of invertebrate gap junctions. Within the nervous system, gap junctions often function as electrical synapses, providing a means for coordinating activity among electrically coupled neurons. While some gap junctions allow the bidirectional flow of small molecules/ions between coupled cells, others permit flow in one direction only or preferentially. The complement of innexins present in a gap junction determines its specific properties. Thus, understanding innexin diversity is key for understanding the full potential of electrical coupling in a species/system. The decapod crustacean cardiac ganglion (CG), which controls cardiac muscle contractions, is a simple pattern-generating neural network with extensive electrical coupling among its circuit elements. In the lobster, Homarus americanus, prior work suggested that the adult neuronal innexin complement consists of six innexins (Homam-Inx1-4 and Homam-Inx6-7). Here, using a H. americanus CG-specific transcriptome, we explored innexin complement in this portion of the lobster nervous system. With the exception of Homam-Inx4, all of the previously described innexins appear to be expressed in the H. americanus CG. In addition, transcripts encoding seven novel putative innexins (Homam-Inx8-14) were identified, four (Homam-Inx8-11) having multiple splice variants, e.g., six for Homam-Inx8. Collectively, these data indicate that the innexin complement of the lobster nervous system in general, and the CG specifically, is likely significantly greater than previously reported, suggesting the possibility of expanded gap junction diversity and function in H. americanus.


Syndrome X, depression, and chaos: relevance to medical practice.
The low detection rate and undertreatment of depression in general medical practice is pervasive. The persistence of this problem suggests that doubt remains within elements of the medical profession that depression is a medical condition meriting medical treatment, as opposed to an existential state, inevitable for the human condition. Depression is a physical and psychological clinical disorder which affects every aspect of human physiology. As such it deserves consideration as a comorbid medical illness requiring treatment as does hypertension in relation to diabetes. This article will illustrate how clinical depression is a comorbid medical illness requiring detection and treatment through the analysis of depression's impact on two conditions called Syndrome X. Conditions labeled Syndrome X in endocrinology and cardiology demonstrate how depression amplifies the pathophysiology of endocrine and cardiac disease and diminishes functional variability (regularizes variance) found in normal physiology.


Finite element analysis of the contact interface between trans-femoral stump and prosthetic socket.
Transfemoral amputees need prosthetic devices after amputation surgery, and the interface pressure between the residual limb and prosthetic socket has a significant effect on an amputee's satisfaction and comfort. The purpose of this study was to build a nonlinear finite element model to investigate the interface pressure between the above-knee residual limb and its prosthetic socket. The model was three-dimensional (3D) with consideration of nonlinear boundary conditions. Contact analysis was used to simulate the friction conditions between skin and the socket. The normal stresses up to 80.57 kPa at the distal end of the soft tissue. The longitudinal and circumferential shear stress distributions at the limb-socket interface were also simulated. This study explores the influences of load transfer between trans-femoral residual limb and its prosthetic socket.


The Center for Alternatives to Animal Testing - Europe (CAAT-EU): a transatlantic bridge for the paradigm shift in toxicology.
The Center for Alternatives to Animal Testing - Europe (CAAT-EU) was founded based collaboration between the Johns Hopkins Bloomberg School of Public Health and the University of Konstanz. CAAT-EU, housed at the University of Konstanz, will coordinate transatlantic activities to promote humane science in research and education, and participate, as partner or coordinator, in publicly and privately funded European projects. Thomas Hartung will serve as program liaison representing Johns Hopkins University and Marcel Leist as the University of Konstanz liaison. CAAT-EU aims to: 1) Set up transatlantic consortia for international research projects on alternative methods. 2) Establish a CAAT Europe faculty and advisory board composed of sponsor representatives and prominent academics from Europe . 3) Participate in the Transatlantic Think Tank for Toxicology (t4) devoted to conceptual work for the paradigm shift in toxicology. 4) Coordinate a series of information days in Europe on relevant developments in the US, similar to the 2009 series CAAT held in the US on EU issues (one on the 7th Amendment to the EU Cosmetics Directive and one on EU and US chemical regulation). 5) Support ALTEX as the official journal of CAAT and CAAT-EU. 6) Develop strategic projects with sponsors to promote humane science and new toxicology, especially with CAAT faculty members. 7) Develop a joint education program between Johns Hopkins and the University of Konstanz, such as e-courses and the existing Humane Science Certificate program developed by CAAT, a student exchange program, and collaboration with the International Graduate School "Cell-based Characterization of De- and Regeneration" in Konstanz.


The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma.
MAP2K1/2 genes are mutated in approximately 8% of melanoma patients; however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. This study focused on the correlation between MAP2K1/2 gene mutations and the treatment response. Six metastatic melanoma clinical cohorts treated with immune checkpoint inhibitors [anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) or anti-programmed cell death-1 (PD-1)] were recruited in this study. RNA expression profiling results from each of these six cohorts and the Cancer Genome Atlas (TCGA) melanoma cohort were analysed to explore the mechanism related to immune activation. Compared to patients with wild-type MAP2K1/2, those with MAP2K1/2 mutations in an independent anti-CTLA-4-treated cohort had higher objective response rates, longer progression-free survival, and longer overall survival (OS). These findings were further validated in a pooled anti-CTLA-4-treated cohort in terms of the OS. However, there was no correlation between MAP2K1/2 mutations and OS in the anti-PD-1-treated cohort. Subgroup Cox regression analysis suggested that patients with MAP2K1/2 mutations received fewer benefits from anti-PD-1 monotherapy than from anti-CTLA-4 treatment. Furthermore, transcriptome profiling analysis revealed that melanoma tumours with MAP2K mutation was enriched in CD8+ T cells, B cells, and neutrophil cells, also expressed high levels of CD33 and IL10, implying a potential mechanism underlying the benefit of melanoma patients with MAP2K1/2 mutations from anti-CTLA-4 treatment. MAP2K1/2 mutations were identified as an independent predictive factor for anti-CTLA-4 therapy in melanoma patients. Anti-CTLA-4 treatment might be more effective than anti-PD-1 therapy for patients with MAP2K1/2-mutated melanoma.


Pd@Bi2Ru2O7/BiVO4 Z-Scheme Heterojunction Nanocomposite Photocatalyst for the Degradation of Trichloroethylene.
Photocatalytic degradation of chlorinated persistent organic pollutants is a very challenging process due to the high redox potential of the C-Cl bond that requires wide band gap catalysts that are activated under UV light. Designing a Z-scheme heterojunction between visible light-activated metal oxides with compatible band gaps enables these redox potentials. Herein, we report the design of a pyrochlore/Aurivillius Z-scheme heterojunction to enhance the photocatalytic activity of BiVO4 for the degradation of trichloroethylene. We prepared Bi2Ru2O7/BiVO4 heterostructured photocatalysts by a controlled hydrothermal approach. Upon optimizing the Bi2Ru2O7 ratio to 1.0 wt %, the heterostructured photocatalyst demonstrated enhanced activity in the degradation of trichloroethylene (TCE) under simulated sunlight irradiation compared to bare BiVO4 and Bi2Ru2O7, respectively. Decorating the surface of the catalyst with palladium nanodomains to create the Pd@Bi2Ru2O7/BiVO4 nanocomposite showed a substantial increase in the photocatalytic degradation of TCE. The material characterization indicated that the architecture of the material provides a synergy of enhancing the redox potential of the photocatalyst and improving the charge carrier dynamics. Furthermore, the photoelectrochemical characterization confirmed that the dual heterojunctions in the Pd@Bi2Ru2O7/BiVO4 nanocomposite resulted in improved interfacial charge carrier transfer and enhanced the electron/hole separation efficiency compared to the nonpalladized catalysts. This work provides a promising approach for band gap engineering of visible light photocatalysts for the degradation of halogenated persistent organic pollutants.


Brief cognitive behavioral intervention for children and adolescents with persistent post-concussive symptoms: A pilot study.
This study aims to evaluate the efficacy of a brief cognitive behavioral intervention program for children and adolescents experiencing persistent post-concussion symptoms. A total of 31 patients aged 10 to 18 years participated in the intervention. The median time since injury at treatment onset was 95 days though the range was large (23-720 days). Treatment was on average four sessions in duration. Sessions included concussion education, activity scheduling, sleep hygiene relaxation training, and cognitive restructuring. Outcomes were measured using symptom reports on the Sports Concussion Assessment Tool - Third Edition (SCAT-3) and parent-reported quality of life on the Pediatric Quality of Life Inventory (PedsQL). Mixed-effects models revealed that symptom reports did not decrease prior to the initiation of this treatment, though significant symptom improvement occurred following treatment. Quality of life scores significantly improved across domains, with the largest gains made in the emotional and school domains. Participant characteristics including age, sex, maternal education, and previous mental health problems were not found to be significantly related to treatment outcomes. Contrary to predictions, length of time since injury was not related to symptom changes. The primary limitation of this study is that it lacks randomization and an experimental control group. The results suggest that brief cognitive behavioral intervention may be a promising treatment for children and adolescents experiencing persistent post-concussive symptoms and warrants further investigation.


Current status of targeted therapies for mantle cell lymphoma.
Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL) with treatment outcomes that have historically been poorer than those observed with other NHL subtypes. Patients typically present with advanced-stage disease and frequent extranodal involvement; the median age at diagnosis is >60 years. Recent improvements in progression-free and overall survival have been observed with more dose-intensive strategies, although at least half of patients diagnosed with MCL are not eligible for such treatment approaches based on age and co-morbidities. In addition, therapy options for relapsed MCL are limited. Only bortezomib is approved for treatment of relapsed MCL in the US. Development of targeted therapy approaches to minimize toxicities while preserving anti-neoplastic properties is of particular importance in MCL. Multiple ongoing studies are attempting to build on the known efficacy of bortezomib by evaluating combination regimens with other targeted agents or cytotoxic chemotherapy. The mammalian target of rapamycin (mTOR) inhibitor temsirolimus has known activity in MCL, making this an attractive class of agents for further investigation in combination regimens. Rituximab and other monoclonal antibodies are being evaluated for novel roles in MCL treatment, including as maintenance therapy. Other classes of drugs being investigated in MCL are immunomodulatory agents, inhibitors of the phosphoinositide 3-kinase/Akt and B-cell receptor signalling pathways, and inhibitors of bcl-2 and histone deacetylase. Although many of the agents appear to have modest single-agent activity, the favourable toxicity profile of many agents will make them best suited for incorporation into combination regimens.


Circling behavior following unilateral microinjections of cocaine into the medial prefrontal cortex: dopaminergic or local anesthetic effect?
Dopaminergic projections to the medial prefrontal cortex have been implicated in cocaine reinforcement; therefore, it was of interest to examine the locomotor effects of acute administration of cocaine to this area. Circling behavior was assessed following injections of 1.0 microliter of cocaine in doses of 0 (0.9% saline), 25, 50, and 100 micrograms/microliters into the medial prefrontal cortex of rats prepared with chronic unilateral guide cannulae. Animals were scored during four 5 min intervals of a 60 min test session that began with the central injection and placement in a flat circular arena. Cocaine was found to produce dose-dependent contraversive circling, an effect previously seen with the dopamine (DA) agonists LY 14 1865 and (+)-amphetamine, suggesting a unilateral stimulant effect. However, since cocaine has potent local anesthetic properties that have been reported to produce behavioral effects and also to inhibit the reuptake of norepinephrine and 5-HT, it was important to demonstrate that the directional bias was a dopaminergic effect. Intra-frontocortical microinjections of the local anesthetic procaine (10, 100, and 1000 micrograms in 0.5 microliter) did not induce circling. Sulpiride (0.001-10.0 micrograms in 0.5 microliter), a DA antagonist specific for the D-2 receptors, produced ipsiversive circling in a dose-dependent manner in rats treated with (+)-amphetamine (1.5 mg/kg, i.p.). In addition, sulpiride (1.0 micrograms in 0.5 microliter) blocked the circling behavior induced by cocaine (50 micrograms in 0.5 microliter) when administered into the medial prefrontal cortex 15 min prior to the cocaine injection. These results provide further evidence for an excitatory influence of mesocortical DA on motor control.


Recent Progress on Functional Genomics Research of Enterovirus 71.
Enterovirus 71 (EV71) is one of the main pathogens that causes hand-foot-and-mouth disease (HFMD). HFMD caused by EV71 infection is mostly self-limited; however, some infections can cause severe neurological diseases, such as aseptic meningitis, brain stem encephalitis, and even death. There are still no effective clinical drugs used for the prevention and treatment of HFMD. Studying EV71 protein function is essential for elucidating the EV71 replication process and developing anti-EV71 drugs and vaccines. In this review, we summarized the recent progress in the studies of EV71 non-coding regions (5' UTR and 3' UTR) and all structural and nonstructural proteins, especially the key motifs involving in viral infection, replication, and immune regulation. This review will promote our understanding of EV71 virus replication and pathogenesis, and will facilitate the development of novel drugs or vaccines to treat EV71.


Deletion of SHATI/NAT8L increases dopamine D1 receptor on the cell surface in the nucleus accumbens, accelerating methamphetamine dependence.
In a previous report, we identified a novel molecule, SHATI/NAT8L, having an inhibitory effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and conditioned place preference (CPP). SHATI/NAT8L attenuates the METH-induced increase in dopamine overflow in the nucleus accumbens (NAc) by promoting plasmalemmal and vesicular dopamine uptake. However, the biological functions of the protein remain unclear. In this study, we explored NAT8L-binding proteins using pull-down assays and identified a number of components of the adaptor protein (AP)-2 complex, which is a multimeric protein localized to the plasma membrane that functions to internalize cargo during clathrin-mediated endocytosis. To investigate whether NAT8L regulates the receptor localization to the cell surface, cell-surface dopamine D1 receptor in the NAc of Nat8l knockout (KO) mice was quantified. We found that dopamine D1 receptor on the cell surface was increased in the NAc of Nat8l KO mice compared with the wild type (WT) animals. Consistent with this finding, Nat8l KO mice showed higher basal locomotor activity and heightened sensitivity to D1 agonist compared with WT mice. In addition, METH-induced sensitization and CPP were enhanced in Nat8l KO mice. These results suggest that NAT8L might regulate the localization of cell-surface dopamine D1 receptor, thereby controlling basal behaviour and sensitivity to METH. Furthermore, we observed a single nucleotide polymorphism (SNP) in the human NAT8L gene related to reward dependence, a personality trait, and grey matter volume in the caudate nucleus in healthy subjects, suggesting that NAT8L might also affect human personality.


Behavior development in the dog: an interspecific analysis.
Young dogs were maintained in isolation from other dogs and under varying degrees of exposure to an alien species (mature rabbits). Parametric observations indicate that an interspecific social attachment develops during the initial hours of co-habitation. The later social interaction patterns of the dogs were influenced, but not irrevocably fixed, by the early cross-specific rearing experience.


[Analysis of the effect of increasing electrodermal stimulation on the somatovegetative reactions evoked by stimulation of the ventromedial hypothalamus].
The influence of increasing electrodermal stimulation (EDS) on the dynamics of the somatovegetative reactions evoked by electrical stimulation of negative emotiogenic regions of the hypothalamus was studied. EDS produced a blocking effect on the somatovegetative reactions evoked by stimulation of the ventromedial hypothalamus (VMH). Pretreatment with naloxone prevented the effects of EDS. Injection of beta-endorphine in a dose of 10 micrograms to the lateral ventricules of the animal brain also blocked the somatovegetative reactions during VMH stimulation. Injection of beta-endorphine in doses of 50-100 micrograms enhanced and prolonged the somatovegetative reactions evoked by VMH stimulation. Elevated arterial blood pressure, pronounced bradycardia, extrasystoles, muscle tremor, and pathologic respiration were recorded. These disorders were completely reversed by EDS. It is assumed that both opiate peptides and their receptors are involved in the mechanism of the somatovegetative reactions evoked by VMH stimulation, experiencing the influence of EDS.


Asymptomatic carriage of Cryptococcus neoformans in the nasal cavity of the koala (Phascolarctos cinereus).
Over a 22-month period, sequential nasal and skin swabs were obtained from 52 healthy captive koalas (Phascolarctos cinereus) from the Sydney region. Cryptococcus neoformans was isolated in 17 koalas from 64 of 262 (24%) nasal swabs and from nine of 262 (3%) skin swabs. Prevalence of nasal colonization varied seasonally from 12% (3/25) to 38% (10/26). Cryptococcus neoformans var. gattii alone was cultured from 37, var. neoformans alone from 22 and both varieties from five nasal swabs. Of 33 koalas sampled on three or more occasions, organisms were isolated persistently from six, occasionally from eight and never from 19. Two koalas were persistently and heavily (>/=100 colonies/plate) colonized by C. neoformans var. gattii and two with var. neoformans. Isolation of C. neoformans var. gattii from the skin was low grade and sporadic. No koalas from which C. neoformans was persistently isolated showed clinical signs of cryptococcosis and all except one had a negative latex cryptococcal antigen test, therefore the nasal cavity was presumed to be colonized by, rather than infected with, C. neoformans. Preliminary observations of koalas from Coffs Harbour indicated a much higher prevalence of colonization by C. neoformans, suggesting that environmental factors influenced the extent of carriage by C. neoformans.


Phenylalanine tolerance test in parents of phenylketonurics.
Phenylalanine tolerance test was carried out in three parents of phenylketonurics and the results compared with the test carried out in control subjects. Compared to the controls, the parents showed a delayed clearance of phenylalanine levels in blood. The findings indicate that this test could be used to detect heterozygote carriers.


Features of the Choroidal Structures in Myopic Children Based on Image Binarization of Optical Coherence Tomography.
To evaluate the features of the choroidal structures in the eyes of myopic children obtained by enhanced depth imaging optical coherence tomography (EDI-OCT). Ninety-six myopic children with low to moderate myopia (spherical equivalent refractive error [SER], -5.75 to -1.00 diopter) were included in this cross-sectional study. Ocular biometrics were measured using an optical low-coherence reflectometry device. Data of the choroidal structures extracted from a 7500-µm cross-sectional arc of the choroid extending from the temporal optic disc margin, including the total choroidal area, luminal area, stromal area, and choroidal vascularity index, were determined by image binarization of the EDI-OCT. Associations between demographic factors, ocular parameters, and choroidal structures were evaluated using univariate and multiple linear regression analyses. The study participants (mean age, 11.02 ± 1.70 years) had a mean axial length (AL) of 24.94 ± 0.70 mm. The mean total choroidal area was 2.64 ± 0.49 mm2 (luminal area, 1.68 ± 0.32 mm2; stromal area, 0.95 ± 0.19 mm2), and the choroidal vascularity index was 0.64 ± 0.03. Multiple regression analysis showed that the luminal area was significantly associated with the AL (standard β = -0.24, P = 0.022) after adjusting for sex and corneal radius (CR), whereas the stromal area (standard β = -0.30, P = 0.003) and choroidal vascularity index (standard β = 0.36, P = 0.001) were significantly associated with age after adjusting for sex, CR, and lens thickness (LT). Sex, CR, LT, and SER showed no significant association with choroidal structures after adjusting for age and AL (all P > 0.05). The luminal area of the choroid tends to decrease with a longer AL, whereas the stromal area tends to decrease with increasing age in myopic children. These findings require further exploration in a longitudinal study.


Human retroviral env and gag polypeptides: serologic assays to measure infection.
Humoral antiviral responses to human retrovirus infections identify persistently infected individuals and can be used to characterize virus-host interactions. Antibodies to native viral polypeptides have been reliably measured, although quantitation of env antibodies is difficult due to a lack of purified antigens. To quantitate antibodies to env antigens, bacterially expressed cloned env polypeptides from the transmembrane regions of human T lymphotropic virus types I and III were applied to nitrocellulose filters in an immunodot assay. A combination of the sensitivity of the Western blot procedure and the specificity of peptides from defined viral sequences was used to detect 49/49 HTLV-III/LAV-infected individuals previously defined as seropositive by radioimmunoprecipitation sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Of these HTLV-III/LAV envelope seropositive people, 22% lacked antibody to p24 in a radioimmunoassay. In contrast, the sensitivity of antibody detection to HTLV-I env antigens and p24 were comparable. Antibodies to HTLV-I and HTLV-III/LAV env transmembrane peptides were not cross-reactive. Levels of antibody to env antigens of both HTLV-I and HTLV-III/LAV persisted without change for at least 26 mo, suggesting that most infections represent stable virus-host interactions. The use of bacterially expressed env peptides offers a rapid serologic approach for distinguishing human retroviral infections and can be used to define immune responses to specific regions of the viral genome.


Vigour reduction in girdled peach trees is related to lower midday stem water potentials.
Stem or trunk girdling is a technique used in physiological studies and in horticultural practice for interrupting carbon flow through the phloem to other parts of the plant without influencing water flow in the xylem. Trunk girdling in peaches is practiced primarily to stimulate fruit growth but it also tends to decrease shoot vigour for a period of time after girdling. Water flow through the trunk or branches of peach trees is thought to be primarily dependent on the most recently formed ring of xylem and vegetative growth is closely related to stem water potential and stem hydraulic conductance. The aim of the present work was to determine whether vigour reduction due to girdling was correlated with a reduction in midday stem water potential during the period of time between girdling and the subsequent healing of stem tissue. 'Springcrest' peach trees were girdled on two different dates. Fruit yield and size, water sprout growth, proleptic shoot growth and stem water potential were measured. Early and late girdled trees yielded larger fruits and fewer and shorter water sprouts in comparison with control trees. Midday stem water potential declined significantly after girdling and gradually recovered until the time of fruit harvest. These results suggest that the vigour reduction of girdled trees is related to a decrease of midday stem water potential caused by girdling. Early tree girdling increased the reduction in midday stem water potential and shoot growth compared with the later girdling treatment. These results point out that even though girdling only removes bark and phloem tissue it can apparently affect water flow in xylem.


Effects of volitional contraction on intracortical inhibition and facilitation in the human motor cortex.
Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) were assessed in the cortical motor area of the first dorsal interosseous muscle (FDI) of 16 healthy subjects. Paired-pulse TMS was delivered to the left hemisphere at the following interstimulus intervals (ISIs): 2 and 3 ms for SICI, 10 and 15 ms for ICF and 1-5 ms for SICF. Motor-evoked potentials were recorded from the resting and active right FDI. The effects exerted on SICI and ICF by four intensities (60-90% of active motor threshold, AMT) of the conditioning stimulus (S1) and by three levels of muscle contraction (10%, 25%, 50% of maximal voluntary contraction, MVC) were evaluated. The effects exerted on SICF were evaluated with two intensities (90% and 70% of AMT) of the test stimulus (S2) and with the same levels of muscle contraction. Results showed that: (i) during 10% MVC, maximum SICI was observed with S1 = 70% AMT; (ii) the amount of SICI obtained with S1 = 70% AMT was the same at rest as during 10% MVC, but decreased at higher contraction levels; (iii) ICF was observed only at rest with S1 = 90% AMT; (iv) SICF was facilitated at 10% and 25% MVC, but not at 50% MVC. We conclude that during muscle activation, intracortical excitability reflects a balance between activation of SICI and SICF systems. Part of the reduction in SICI during contraction is due to superimposed recruitment of SICF. Low intensity (70% AMT) conditioning stimuli can test SICI independently of effects on SICF at low contraction levels.


Biological and clinical heterogeneity of B-cell chronic lymphocytic leukemia.
B-cell chronic lymphoproliferative disorders have been recognized as a heterogeneous group of neoplastic diseases affecting the lymphoid system. They are frequently characterized by leukemic manifestations with peripheral blood and/or bone marrow involvement. B-cell chronic lymphocytic leukemia (B-CLL), a disease which is now accepted as derived from immunologicallycompetent antigen-activated B-cells, is the most common in the western countries. Although for several decades it was considered as a unique entity, a body of evidences is now emerging indicating the biological heterogeneity of B-CLL. Molecular and immunophenotypic data induce to consider two main subgroups of B-CLL exist at the cellular level: in fact, B-CLL cases can be divided into two categories according to IgV gene mutation status. One group develops from "memory" B-cells after antigenic stimulation in the germinal center of secondary follicles, displays mutated gene IgV and lacks CD38 expression; the second one derives from the so-called "naïve" antigen inexperienced B-cells, does not present IgV gene mutations and displays CD38 surface molecule. The two groups seem to be characterised by different clinical outcomes with the "mutated" group expected to have a more benign course than that arising from a "naïve" B-cell. Thus, the definition of the biological features of these different groups could be of help for clinicians in order to recognize patients needing more intensive therapeutic approaches.


Myocyte-derived Myomaker expression is required for regenerative fusion but exacerbates membrane instability in dystrophic myofibers.
Muscle progenitor cell fusion is required for the formation and regeneration of multinucleated skeletal muscle fibers. Chronic muscle regeneration in Duchenne muscular dystrophy (DMD) is characterized by ongoing fusion of satellite cell (SC) progeny, but the effects of fusion on disease and the mechanisms by which fusion is accomplished in this setting are not fully understood. Using the mdx mouse model of DMD, we deleted the fusogenic protein Myomaker in SCs or myofibers. Following deletion in SCs, mice displayed a complete lack of myocyte fusion, resulting in severe muscle loss, enhanced fibrosis, and significant functional decline. Reduction of Myomaker in mature myofibers in mdx mice, however, led to minimal alterations in fusion dynamics. Unexpectedly, myofiber-specific deletion of Myomaker resulted in improvement of disease phenotype, with enhanced function and decreased muscle damage. Our data indicate that Myomaker has divergent effects on dystrophic disease severity depending upon its compartment of expression. These findings show that myocyte fusion is absolutely required for effective regeneration in DMD, but persistent Myomaker expression in myofibers due to ongoing fusion may have unintended deleterious consequences for muscle integrity. Thus, sustained activation of a component of the myogenic program in dystrophic myofibers exacerbates disease.


Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells.
Polymorphisms in several DNA repair genes have recently been identified, but little is known about their phenotypic significance. To determine whether variation in DNA repair genes is related to host DNA damage, we studied the association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 751) and two markers of DNA damage, sister chromatid exchange (SCE) frequencies (n = 76) and polyphenol DNA adducts (n = 61). SCE frequencies were determined using a modified fluorescence-Giemsa method and polyphenol DNA adducts were determined using a P1-enhanced (32)P-post-labeling procedure. XRCC1 and ERCC2 genotypes were identified using PCR-RFLP. Mean SCE frequencies among current smokers who were homozygous carriers of the 399Gln allele in XRCC1 were greater than those in 399Arg/Arg current smokers. We also observed a possible gene-dosage effect for XRCC1 399Gln and detectable DNA adducts, and significantly more adducts among older subjects who were carriers of the 399Gln allele than in younger subjects with the 399Arg/Arg genotype. The polymorphism in ERCC2 was unrelated to SCE frequency or DNA adduct level. Our results suggest that carriers of the polymorphic XRCC1 399Gln allele may be at greater risk for tobacco- and age-related DNA damage.


Coexpression of the B subunit of Shiga toxin 1 and EaeA from enterohemorrhagic Escherichia coli in Vibrio cholerae vaccine strains.
A promoterless gene for the Shiga toxin 1 B subunit (stxB1) has been placed under transcriptional control of the Vibrio cholerae heat shock gene htpG. A chromosomal enterohemorrhagic Escherichia coli fragment containing eaeA and 400 bp of upstream DNA was added to the construct, downstream of stxB1; no transcription terminators were located between the two genes. The plasmid construct was confirmed by DNA sequencing; in vitro transcription-translation studies demonstrated expression of EaeA from the plasmid. The htpGp-->stxB1, eaeA construct was inserted into lacZ on the chromosome of Peru2, an El Tor V. cholerae strain with both attRS1 sequences and the entire cholera toxin genetic element deleted, and into lacZ in JRB10, a Peru2 derivative that has a second copy of htpGp-->stxB1 also inserted in the V. cholerae virulence gene irgA. Two plasmid constructs, one containing stxB1 under the control of the tac promoter and another containing htpGp-->stxB1,eaeA, were transformed into Peru2. Expression of StxB1 by these constructs was quantified by enzyme-linked immunosorbent assay and was highest in the plasmid construct with stxB1 under the control of the tac promoter. Localization of EaeA to the outer membrane of the vector strains was demonstrated both by Western blotting and by immunofluorescence with an anti-EaeA antibody. A rabbit model for colonization by V. cholerae was used to compare the immune responses to the two heterologous antigens, StxB1 and EaeA, expressed by these strains. Rabbits immunized with Peru2 transformed with a plasmid carrying tac-->stxB1 developed neutralizing serum anti-StxB1 immunoglobulin G antibody responses. One of two rabbits immunized with a strain carrying a chromosomal copy of eaeA developed a marked immune response against EaeA. The plasmid construct containing htpGp-->stxB1,eaeA was unstable, producing low levels of StxB1 in vitro and not evoking anti-EaeA antibody responses in vivo following oral immunization. Chromosomal insertion of eaeA may be preferred for future expression of this antigen in V. cholerae vaccine constructs.


Breaking the silence: South African HIV policies and the needs of men who have sex with men.
Although the HIV epidemic among men who have sex with men (MSM) in South Africa preceded the onset of the generalised HIV epidemic by several years, current policies and programmes focus on heterosexual transmission and mother-to-child transmission. We used an adaptation of the UNAIDS Country Harmonised Alignment Tool (CHAT) to assess whether existing HIV policies and programmes in South Africa address the needs of MSM. This covered mapping of key risk factors and epidemiology of HIV among MSM; participation of MSM in the HIV response; and an enabling environment for service provision, funding and human resources. We found that current policies and programmes are unresponsive to the needs of MSM and that epidemiologic information is lacking, in spite of policy on MSM in the National Strategic Plan. We recommend that government initiate sentinel surveillance to determine HIV prevalence among MSM, social science research on the contexts of HIV transmission among MSM, and appropriate HIV prevention and care strategies. MSM should be closely involved in the design of policies and programmes. Supportive programme development should include dedicated financial and human resources, appropriate guidelines, and improved access to and coverage of HIV prevention, treatment and care services for MSM.


[The general patterns in the development of the ultrastructural reactions under the action of electromagnetic radiations].
Original investigations of the author provided authors with information on subcellular adaptive reactions in response to electromagnetic radiation. Activation of hyperplastic processes represents the leading structural-adaptive response of the body arising accelerated renewal of the ultrastructures. The author characterizes adaptive hyperplasia of the ultrastructures. The author characterizes adaptive hyperplasia emerging in bioenergetic and protein-synthetizing organelles in the cells of different organs. It is emphasized that high intensities provoke destructive processes.


Inhibition of CYP2E1 reverses CD4+ T-cell alterations in trichloroethylene-treated MRL+/+ mice.
Trichloroethylene is an organic solvent that is primarily used as a degreasing agent for metals. There is increasing evidence in both humans and animal models that trichloroethylene promotes the development of autoimmunity, but little is known about the mechanisms that mediate the effect of trichloroethylene on the immune system. Metabolic activation of trichloroethylene is considered an obligatory pathway for other known toxicities such as hepatotoxicity, nephrotoxicity, and carcinogenicity. Trichloroethylene is metabolized by the cytochromes P450, primarily cytochrome P450 2E1 (CYP2E1). To investigate whether metabolism by CYP2E1 is required for immunomodulation, we treated autoimmune prone MRL+/+ mice with trichloroethylene in the drinking water for 4 weeks, in the presence or absence of diallyl sulfide, a specific inhibitor of CYP2E1. Using an antibody that recognizes proteins covalently modified by a reactive metabolite of trichloroethylene; two immunoreactive proteins were detected in liver microsomes from trichloroethylene-treated mice. Formation of these trichloroethylene-protein adducts, an indicator of metabolic activation, was completely inhibited in animals that were concomitantly treated with trichloroethylene and diallyl sulfide. The level of CYP2E1 apoprotein in liver microsomes was significantly reduced in the presence of diallyl sulfide. The enhanced mitogen-induced proliferative capacity of T cells from trichloroethylene-treated MRL+/+ mice was inhibited if the mice were also treated with diallyl sulfide. In addition, the reduction in interleukin-4 levels secreted by activated CD4+ T cells from trichloroethylene-treated mice was reversed if the mice were also treated with diallyl sulfide. Taken collectively, metabolism of trichloroethylene by CYP2E1 is responsible, at least in part, for the CD4+ T cell alterations associated with exposure to this environmental toxicant.


Biofilms formed by nontypeable Haemophilus influenzae in vivo contain both double-stranded DNA and type IV pilin protein.
Nontypeable Haemophilus influenzae (NTHI) strains are members of the normal human nasopharyngeal flora, as well as frequent opportunistic pathogens of both the upper and lower respiratory tracts. Recently, it has been shown that NTHI can form biofilms both in vitro and in vivo. NTHI strains within in vitro-formed biofilms differentially express both epitopes of lipooligosaccharide (LOS) and the outer membrane proteins P2, P5, and P6, whereas those generated either in a 96-well plate assay in vitro or in a mammalian host have been shown to incorporate a specific glycoform of sialylated LOS within the biofilm matrix. While DNA has been identified as a key component of the biofilm matrix formed in vitro by several bacterial pathogens, here we demonstrate for the first time that in addition to sialylated LOS, the biofilm formed by NTHI in vivo contains both type IV pilin protein and a significant amount of double-stranded DNA. The DNA appeared to be arranged in a dense interlaced meshwork of fine strands as well as in individual thicker "ropes" that span water channels, suggesting that DNA could be imparting structural stability to the biofilm produced by NTHI in vivo. The presence of type IV pilin protein both appearing as small aggregates within the biofilm matrix and tracking along DNA strands supports our observations which showed that type IV pili are expressed by NTHI during experimental otitis media when these bacteria form a biofilm in the middle ear space.


High Interleukin-37 (IL-37) Expression and Increased Mucin-Domain Containing-3 (TIM-3) on Peripheral T Cells in Patients with Rheumatoid Arthritis.
BACKGROUND Anti-inflammatory mediators such as mucin-domain containing-3 (TIM-3) and IL-37 play an important role in the regulation of Th1-mediated immunity. This study was designed to investigate the proportions of various T cell subsets and monocytes in the peripheral blood of rheumatoid arthritis (RA) patients, as well as the level of TIM-3 on these cells and serum cytokine levels. MATERIAL AND METHODS We enrolled 59 RA patients and 46 age- and sex-matched healthy controls in this study. The proportion of T cells and TIM-3 expression on these T cells were determined by flow cytometry. Cytokine levels in serum were determined by ELISA. RESULTS Compared with the healthy controls, the proportions of CD3+CD4+ T cells and CD3+CD4+CD25+CD127low T cells in the peripheral blood were significantly higher in RA patients. However, RA patients had significantly lower proportions of CD3+CD8+ T cells and CD3+CD4-CD8- T cells. TIM-3 was highly expressed on CD3+CD4+, CD3+CD8+, CD3+CD4+CD25+CD127low, and CD3+CD4-CD8- T cells, as well as CD14+ monocytes, in RA patients. Nevertheless, no correlation between TIM-3 level and an RA disease activity score of 28 was found. The elevated serum levels of IL-6 and IL-37 were positively correlated with tumor necrosis factor-α (TNF-α). CONCLUSIONS Both pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory mediators (TIM-3 and IL-37) simultaneously contribute to the pathogenesis of RA. TIM-3 and IL-37 may be used as potential biomarkers of active RA.


Characteristics associated with hypersomnia and excessive daytime sleepiness identified by extended polysomnography recording.
Hypersomnolence, defined by excessive daytime sleepiness (EDS) or excessive quantity of sleep (EQS), has been associated with increased morbidity. The aim of this study was to determine the clinical and polysomnographic characteristics associated with EQS and EDS assessed objectively during extended polysomnography recording. A total of 266 drug-free subjects (201 women; mean age: 26.5 years [16.08; 60.87]) underwent 32-h bed-rest polysomnography recording preceded by polysomnography and modified multiple sleep latency test (mMSLT). Participants were categorized according to their total sleep time (bed-rest TST ≥19 h, hypersomnia), objective EDS (mean sleep latency on MSLT ≤8 min), and self-reported EDS (Epworth sleepiness scale score >10) and EQS (≥9 h/24 h per week). Subjects with hypersomnia were often younger, with normal sleep architecture, high nighttime sleep efficiency, and severe objective EDS. No association with sex, body mass index, Epworth sleepiness scale, EQS, and depressive symptoms was detected. Subjects with objective EDS had less EQS, higher sleep efficiency, and increased hypersomnia. Discrepancies were observed between objective and self-reported measures of sleep duration and EDS. Finally, 71 subjects were identified who had objective hypersomnia and/or EDS, no medical and psychiatric conditions and normal polysomnography parameters, and therefore met the stringent criteria of idiopathic hypersomnia, an orphan disorder. Sleep duration and EDS should be quantified using self-reported and objective measures in a controlled procedure to differentiate long sleepers, patients with hypersomnia, and patients with idiopathic hypersomnia. This will help to better understand their biology, to identify specific biomarkers, and to assess related health outcomes.


Evolution of floral scent in relation to self-incompatibility and capacity for autonomous self-pollination in the perennial herb Arabis alpina.
The transition from outcrossing to selfing is a frequent evolutionary shift in flowering plants and is predicted to result in reduced allocation to pollinator attraction if plants can self-pollinate autonomously. The evolution of selfing is associated with reduced visual floral signalling in many systems, but effects on floral scent have received less attention. We compared multiple populations of the arctic-alpine herb Arabis alpina (Brassicaceae), and asked whether the transition from self-incompatibility to self-compatibility has been associated with reduced visual and chemical floral signalling. We further examined whether floral signalling differ between self-compatible populations with low and high capacity for autonomous self-pollination, as would be expected if benefits of signalling decrease with reduced dependence on pollinators for pollen transfer. In a common garden we documented flower size and floral scent emission rate and composition in eight self-compatible and nine self-incompatible A. alpina populations. These included self-compatible Scandinavian populations with high capacity for autonomous self-pollination, self-compatible populations with low capacity for autonomous self-pollination from France and Spain, and self-incompatible populations from Italy and Greece. The self-compatible populations produced smaller and less scented flowers than the self-incompatible populations. However, flower size and scent emission rate did not differ between self-compatible populations with high and low capacity for autonomous self-pollination. Floral scent composition differed between self-compatible and self-incompatible populations, but also varied substantially among populations within the two categories. Our study demonstrates extensive variation in floral scent among populations of a geographically widespread species. Contrary to expectation, floral signalling did not differ between self-compatible populations with high and low capacity for autonomous self-pollination, indicating that dependence on pollinator attraction can only partly explain variation in floral signalling. Additional variation may reflect adaptation to other aspects of local environments, genetic drift, or a combination of these processes.


Selected attributes of polyphenols in targeting oxidative stress in cancer.
Various plant polyphenols have been recognized as redox active molecules. This review discusses some aspects of polyphenols' modes of redox action, corresponding structure-activity relationships and their potential to be applied as adjuvants to conventional cytostatic drugs. Polyphenols' antioxidative capacity has been discussed as the basis for targeting oxidative stress and, consequently, for their chemopreventive and anti-inflammatory activities, which may alleviate side-effects on normal cells arising from oxidative stress caused by cytostatics. Some polyphenols may scavenge various free radicals directly, and some of them are found to suppress free radical production through inhibiting NADPH oxidases and xanthine oxidase. Additionally, polyphenols may increase antioxidative defense in normal cells by increasing the activity of NRF2, transcription factor for many protective proteins. The activation of the NRF2-mediated signaling pathways in cancer cells results in chemoresistance. Luteolin, apigenin and chrysin reduce NRF2 expression and increase the chemosensitivity of cancer cells to cytostatic drugs. Their common 5,7-dihydroxy-4H-chromen-4-one moiety, may represent a starting pharmacophore model for designing novel, non-toxic compounds for overcoming chemoresistance. However, prooxidative activity of some polyphenols (quercetin, EGCG) may also provide a basis for their use as chemotherapeutic adjuvants since they may enhance cytotoxic effects of cytostatics selectively on cancer cells. However, considerable caution is needed in applying polyphenols to anticancer therapy, since their effects greatly depend on the applied dose, the cell type, exposure time and environmental conditions.


Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat.
Adverse events in pregnancy may 'programme' offspring for the later development of cardiovascular disease and hypertension. Previously, using a rodent model of programmed hypertension we have demonstrated the role of the renin-angiotensin system in this process. More recently we showed that a maternal low protein diet resulted in undermethylation of the At1b angiotensin receptor promoter and the early overexpression of this gene in the adrenal of offspring. Here, we investigate the hypothesis that maternal glucocorticoid modulates this effect on fetal DNA methylation and gene expression. We investigated whether treatment of rat dams with the 11beta-hydroxylase inhibitor metyrapone, could prevent the epigenetic and gene expression changes we observed. Offspring of mothers subjected to a low protein diet in pregnancy showed reduced adrenal Agtr1b methylation and increased adrenal gene expression as we observed previously. Treatment of mothers with metyrapone for the first 14 days of pregnancy reversed these changes and prevented the appearance of hypertension in the offspring at 4 weeks of age. As a control for non-specific effects of programmed hypertension we studied offspring of mothers treated with dexamethasone from day 15 of pregnancy and showed that, whilst they had raised blood pressure, they failed to show any evidence of Agtr1b methylation or increase in gene expression. We conclude that maternal glucocorticoid in early pregnancy may induce changes in methylation and expression of the Agtr1b gene as these are clearly reversed by an 11 beta-hydroxylase inhibitor. However in later pregnancy a converse effect with dexamethasone could not be demonstrated and this may reflect either an alternative mechanism of this glucocorticoid or a stage-specific influence.


[Transplantation of the lungs].
The paper is concerned with current status of lung transplantation. The problem was studied by the author in his own experiments, in clinics of Canada and USA. Literature data are reviewed. Special attention is focused on indications for the transplantation, taking and preservation of the transplant, prevention of the rejection, difficulties of clinical introduction of lung transplantation in this country.


Visualization and temporal/spatial characterization of cardiac radiofrequency ablation lesions using magnetic resonance imaging.
The purpose of this study was to describe a system and method for creating, visualizing, and monitoring cardiac radiofrequency ablation (RFA) therapy during magnetic resonance imaging (MRI). RFA was performed in the right ventricular apex of 6 healthy mongrel dogs with a custom 7F nonmagnetic ablation catheter (4-mm electrode) in a newly developed real-time interactive cardiac MRI system. Catheters were positioned to intracardiac targets by use of an MRI fluoroscopy sequence, and ablated tissue was imaged with T2-weighted fast spin-echo and contrast-enhanced T1-weighted gradient-echo sequences. Lesion size by MRI was determined and compared with measurements at gross and histopathological examination. Ablated areas of myocardium appeared as hyperintense regions directly adjacent to the catheter tip and could be detected 2 minutes after RF delivery. Lesions reached maximum size approximately 5 minutes after ablation, whereas lesion signal intensity increased linearly with time but then reached a plateau at 12.2+/-2.1 minutes. Lesion size by MR correlated well with actual postmortem lesion size and histological necrosis area (55.4+/-7.2 versus 49.7+/-5.9 mm(2), r=0.958, P<0.05). RFA can be performed in vivo in a new real-time interactive cardiac MRI system. The spatial and temporal extent of cardiac lesions can be visualized and monitored by T2- and T1-weighted imaging, and MRI lesion size agrees well with actual postmortem lesion size. MRI-guided RFA may be a useful approach to help facilitate anatomic lesion placement and to provide insight into the biophysical effects of new ablation techniques and technologies.


[Living the caring and healing experiences as a family member in a hospital].
This article describes the author's experience in living the care and healing in the family member's perspective in a Private Hospital's Emergency unit. The objective of this article is to reflect about the process of communication and its relevance for the nurse's team, the patient and his family in this unit. Some authors that support the idea that communication is the pathway that express the nursing care were used. We pointed some critical points, suggestions for a possible solution and the importance of nursing in this context.


Clinical significance of exercise-induced ST segment elevation. Correlative angiographic study in patients with ischaemic heart disease.
We have examined the relation between electrocardiographic ST elevation during treadmill exercise (greater than or equal to 1 mm, using the conventional 12 leads), the severity of coronary artery disease, and left ventricular wall motion abnormalities in 680 patients. They were divided into three groups: (1) 218 patients with clinically significant coronary artery disease, (2) 178 patients with clinically significant coronary artery disease, and (3) 284 patients with clinically significant coronary artery disease and previous myocardial infarction. ST elevation during exercise (predominantly in lead V2) was seen in two patients (1%) in group 1, three patients (2%) in group 2, and 147 patients (52%) in group 3. Coronary artery disease (number of vessels involved and severity of stenoses) was comparable in groups 2 and 3. All the patients in group 1 showed a normal left ventricular contraction pattern; 64% of the patients in group 2 showed wall motion abnormalities (predominantly hypokinesia) and 95% of group 3 (mainly akinesia, dyskinesia, or aneurysm). A strongly positive correlation was seen between the ST elevation and left ventricular dysfunction in patients belonging to group 3. The overall sensitivity and the specificity of the stress test in detecting wall motion abnormalities was 55% and 100% respectively. The sensitivity increased with deterioration in left ventricular function, reaching 81% and 90% in patients with dyskinesia and aneurysm, respectively. Maximal ST elevation (greater than or equal to 3 mm) was confined to the patients with dyskinesia or aneurysm. The incidence of ST elevation during exercise was also related to the location of previous infarction, showing a positive response in 85% of patients with anterior myocardial infarction and in only 33% with inferior myocardial infarction. We conclude that ST segment elevation during exercise in patients with previous myocardial infarction is a sensitive and a specific indicator of advanced left ventricular asynergy. The ST segment response during exercise in patients with previous infarction and with angiographically demonstrated myocardial asynergy appears to be a continuous spectrum. A normal ST segment response or elevation alone usually signifies involvement of only one vessel supplying the infarcted myocardium, ST elevation with concomitant ST depression indicates additional coronary artery disease, and ST depression alone indicates overwhelming myocardial ischaemia resulting from multiple vessel disease. The employment of multiple leads is essential to obtain this information.


Nutrient and energy balance, and amino acid digestibility in weaned piglets fed wheat bran and an exogenous enzyme combination.
The digestive system of the weaned piglets can be affected by the type of ingredients present in the diet, and a high fibre content in diets can limit the use of other nutrients and energy. The study was conducted to determine the effects of multicarbohydrase (MC) and phytase (Phy) supplementation on the nutritive value of wheat bran (WB) in weaned piglets. Multicarbohydrase preparation had 700 U α-galactosidase, 2200 U galactomannanase, 3000 U xylanase and 22 000 U β-glucanase per kilogram of diet, and Phy had 500 phytase units - FTU/kg of diet. Twenty-five weaned piglets (6.1 ± 0.63 kg) at 21 days old were fed five diets in a completely randomised experimental design with a 2 × 2 + 1 (0 and 200 mg/kg MC; 0 and 50 mg/kg Phy; and basal diet - BD) factorial arrangement used to determine treatment effects. An additional group of piglets was fed a corn-basal diet during apparent digestibility of nutrients, and fed a 5% casein-corn starch basal diet during apparent and standardised ileal digestibility (SID) of amino acid evaluations. Piglets were individually caged until 38 days old, when Ileal digesta was collected at slaughter. Test diets were made by mixing the basal diets and WB 7 : 3 (w/w), with or without MC, Phy or the combination. There was an interaction trend (P = 0.07) between MC and Phy in the balance of ash, digestible energy (DE) and metabolisable energy (ME). Effects of MC (P < 0.01) on DM, N retention, DE and ME, as well as an effect of Phy (P < 0.05) on ash, DE and ME and a trend in protein digestibility (P = 0.07) also was observed. The enzyme combination showed effect (P < 0.05) on SID of Lys, Pro and Ser; as a trend (P < 0.07) on His, Thr and Val. Isolated, MC also suggested improving (P < 0.07) on SID of His, Lys, Ala (P < 0.05), while Phy improved (P < 0.06) SID of Leu, Lys, Met (P < 0.01), Thr, Val, Ala (P < 0.01), Pro and Ser (P < 0.05). The MC carbohydrate complex was characterised as a viable alternative to increase the apparent nutrients digestibility and SID of amino acids when WB was used in the diet of young pigs and, when combined with Phy, suggested an additive effect on the apparent use of energy.