Occurrence and source of chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) in tidal flats of the Ariake Bay, Japan.
In this study, we hypothesize that natural photochemical reactions of polycyclic aromatic hydrocarbons (PAHs) in tidal flats are responsible for the occurrence of chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs). This study aims to survey the impact of photochemical reactions using a combination of field surveys and lab-scale experiments. Concentrations and profiles of PAHs and Cl-PAHs in road dust and sediments collected from seven tunnels and two watersheds, respectively, were determined. In the lab-scale experiments, anthracene was irradiated with ultraviolet (UV) light under various salinity conditions. No detectable Cl-PAHs were found in the road dust. However, Cl-PAHs were detected in the sediments from 700 to 6.1 × 10(3) pg g(-1) and specifically from downstream sites. 2-Monochloroanthracene (2-Cl-ANT) and 9,10-dichloroanthracene (9,10-di-Cl-ANT) were dominant in the sediments. In the Domen River watershed, the ∑Cl-PAHs and the salinity showed a significant positive correlation (p < 0.01) in the sediments, while such a correlation was not found for PAHs. 2-Cl-ANT, 9-monochloroanthracene, and 9,10-di-Cl-ANT were identified as transformation products in the UV irradiation experiments. Production of these Cl-PAHs was dependent on the solution salinity. These results support our hypothesis, and we conclude that photochemical reactions significantly contribute to the occurrence of Cl-PAHs in the studied tidal flats.


Through the Microbial Looking Glass: Premature Labor, Preeclampsia, and Gestational Diabetes: A Scoping Review.
The influence of microbial factors on adverse perinatal outcomes has become the focal point of recent investigations, with particular interest in the role of the microbiome and probiotic interventions. The purpose of this scoping review was to identify and critique the most recent evidence about these factors as they relate to pregnancies complicated by preeclampsia (PEC), preterm birth (PTB), and gestational diabetes mellitus (GDM). Four databases (PubMed, EMBASE, Web of Science, and Cochrane) were searched for articles published in English in the last 10 years with the concepts of the microbiome, probiotics, and PEC, PTB, or GDM. Forty-nine articles were eligible for full-text review. Five articles were excluded, leaving 44 articles that met all the eligibility criteria. The relationships between the microbiome and the risk for PEC, PTB, and GDM are not fully elucidated, although probiotic interventions seem beneficial in decreasing PEC and GDM risk. Probiotic interventions targeting bacterial vaginosis and elimination of infection in women at risk for PTB appear to be beneficial. More research is needed to understand the contributions of the microbiome to adverse perinatal outcomes. Probiotic interventions appear to be effective in reducing risk for select outcomes.


The sacroiliitis of acute Reiter's syndrome.
Sacroiliitis can be demonstrated radiologically in over one-third of patients with chronic Reiter's syndrome. We have used a bone scan technique with digital analysis which will quantitatively assess the sacroiliac joints, and have found abnormalities in 24 of 33 patients with active Reiter's syndrome. It seems likely therefore that sacroiliitis is a common feature in patients with early Reiter's syndrome and while in most patients it resolves with resolution of disease activity, in some it may persist with the development of overt radiological changes.


An electron microscopic study of antagonism between cephalexin and erythromycin in Staphylococcus aureus.
This study concerns investigations at the cellular level of antagonism between cephalexin (CEX) and erythromycin (EM) with the aid of electron microscopes and a liquid scintillation counter. Exposure of Staphylococcus aureus 209-P to CEX and EM in combination was found to result in a marked antagonism between the two antibiotics in their effects on the growth of the organism. Observations under a scanning electron microscope revealed lysed cells in the presence of CEX alone but almost no lysis in the presence of a combination of CEX and EM. Observations under a transmission electron microscope, on the other hand, disclosed that nearly all of the cells exposed to 20 mug/ml of CEX were transformed into protoplasts with their morphological changes being most marked after 4 hr of exposure. When 1 mug/ml of EM was allowed to act alone, this exposure resulted in thickening of the cell walls. The combined use of CEX and EM, however, resulted in neither thickening of the cell walls as in the presence of EM alone nor in the formation of protoplasts as in the presence of CEX alone but merely produced the swelling of separating walls. Cellular uptake of 14C-L-lysine and N-acetylglucosamine-1-14C into the cell wall fraction and the protein fraction was affected by CEX and EM, respectively, when used alone or in combination.


Involvement of platelet-derived growth factor receptor β in fibrosis through extracellular matrix protein production after ischemic stroke.
Fibrosis is concomitant with repair processes following injuries in the central nervous system (CNS). Pericytes are considered as an origin of fibrosis-forming cells in the CNS. Here, we examined whether platelet-derived growth factor receptor β (PDGFRβ), a well-known indispensable molecule for migration, proliferation, and survival of pericytes, was involved in the production of extracellular matrix proteins, fibronectin and collagen type I, which is crucial for fibrosis after ischemic stroke. Immunohistochemistry demonstrated induction of PDGFRβ expression in vascular cells of peri-infarct areas at 3-7days in a mouse stroke model. The PDGFRβ-expressing cells extended from peri-infarct areas toward the ischemic core after day 7 while expressing fibronectin and collagen type I in the infarct areas. In contrast, desmin and α-smooth muscle actin, markers of pericytes, were only expressed in vascular cells. In PDGFRβ heterozygous knockout mice, the expression of fibronectin and collagen type I was attenuated at both mRNA and protein levels with an enlargement of the infarct volume after ischemic stroke compared with that in wild-type littermates. In cultured brain pericytes, the expression of PDGF-B, PDGFRβ, fibronectin, and collagen type I, but not desmin, was significantly increased by serum depletion (SD). The SD-induced upregulation of fibronectin and collagen type I was suppressed by SU11652, an inhibitor of PDGFRβ, while PDGF-B further increased the SD-induced upregulation. In conclusion, the expression level of PDGFRβ may be a crucial determinant of fibrosis after ischemic stroke. Moreover, PDGFRβ signaling participates in the production of fibronectin and collagen type I after ischemic stroke.


[Preoperative imaging as the basis for image-guided neurosurgery].
With the progressive development of soft- and hardware, the acceptance of image-guided neurosurgery has increased dramatically. Additional image data are required to analyze the nature and the dimensions of pathological processes and the surrounding tissue. In this context, fMRI, SPECT, PET, as well as special modalities of CT and MR imaging, are routinely used. Secondary post-processing options are used to detect intracerebral lesions as well as adjacent functional eloquent regions in the parenchymatous organ pre- and intraoperatively. The integration of different image information guarantees the precise planning and realization of surgical maneuvers. The segmentation of interesting structures and risk structures, as well as their implementation in the neuronavigation systems, help to avoid additional intraoperative traumatization and offer a higher level of safety and precision. In this article the value and limitations of presurgical imaging will be discussed.


Hydro-marking Your Territory: Using a Novel Percutaneous Tagging System to Assist Pulmonary Nodule Identification During Video-assisted Thoracoscopic Surgery.
The management of lung cancer is highly dependent on surgical resection. There are different surgical managements that are utilized on a patient to patient basis. Small lung nodules are particularly difficult to resect and have a higher postoperative complication rate. Video-assisted thoracoscopic surgery is the preferred method of surgery over open thoracotomy, but requires the preoperative percutaneous placement of a marker to help the surgeon identify the nodule once conducting surgical resection. There are various methods to place percutaneous markers, but have reported complications. The following case will present the novel placement of a hydrogel tagging system on a small pulmonary nodule, demonstrating superiority to other methods of percutaneous marker placement.


Effect of tobramycin on fractional sodium excretion in neonates.
Fractional sodium excretion (FENa) was measured in 25 neonates during and after treatment with tobramycin. Mean birthweight of infants was 1.83 kg and mean gestational age was 34.3 weeks. Tobramycin therapy was initiated within 48 hours of birth and levels were maintained within the therapeutic range. Mean FENa values were persistently elevated during treatment and decreased to the normal range within 2 days of stopping antibiotics. Blood urea and creatinine concentrations were normal throughout the period of study. Exposure to the aminoglycoside appears to delay the previously described postnatal decline in FENa, most likely reflecting subtle renal tubular dysfunction.


Self-expanding nanoplatinum-coated nitinol devices for atrial septal defect and patent ductus arteriosus closure: a swine model.
Our purpose was to evaluate self-expanding nanoplatinum-coated nitinol devices for transcatheter closure of atrial septal defects and patent ductus arteriosus in a swine model. The devices were braided from platinum-activated nitinol wires and filled with polyester to enhance thrombogenicity. The platinum activation of the nitinol wires was carried out with the help of Nanofusion technology. The coating of platinum covers the exposed surface of the nitinol wires and prevents the release of nickel into the blood stream after the implantation of the device but does not affect its shape memory, which makes the device self-expanding after it is loaded from the catheter. Atrial septal defects were created in 12 piglets by balloon dilation of the patent foramen ovale. The size of the device was selected on the basis of the diameter of the balloon and the size of the defect, measured by transthoracic echocardiography. The devices were successfully deployed in all 12 piglets under fluoroscopic study. Transthoracic color Doppler echocardiograms showed complete closure of the atrial septal defect within 15 minutes of device implantation. Twelve patent ductus arteriosus closure devices were deployed in the right or left subclavian arteries in 10 piglets. Angiograms showed complete occlusion of the subclavian arteries within a few minutes of device deployment. In the atrial septal defect cases, the autopsy findings showed complete organizing fibrin thrombus formation and complete neo-endothelialization on the outer surface of the devices within one week and six weeks of implantation, respectively. The use of self-expanding nanoplatinum-coated nitinol devices for the transcatheter closure of atrial septal defects and patent ductus arteriosus is feasible. The excellent occlusion result and complete neo-endothelialization of the devices in the swine model is an indication of the potential of these devices in human application.


Decomposition characteristics of humic-like matters with the hollow ellipsoid structure sludge inoculated from decayed soil in mature landfill leachate.
The organics in mature leachate are mainly humic-like matters, which account for over 80% weight of the total organics. In this work, the microorganisms in decayed soil were found to be capable of decomposing the humic-like matters evidently using an anaerobic-aerobic/anoxic bioprocess in two sequencing bio-reactors. The 3D excitation-emission matrix and Fourier transform infrared (FT-IR) were applied to characterize the variation of dissolved organic matters in mature leachate while sludge morphology was characterized by scanning electron microscopy. The intensities of fluorescence peaks A and C of leachate effluents were 71.66% and 48.75% lower than those of influents, respectively, which indicated the extraordinary degradation ability of microorganisms inoculated from the decayed soil. Meanwhile a kind of distinctive hollow ellipsoid structure sludge organized by tiny soil particles was observed, which might favour the humic-like matters' decomposition and has never been reported before as we know. The formation mechanisms of hollow ellipsoid structure sludge will need further study.


A fast, efficient chromatin immunoprecipitation method for studying protein-DNA binding in Arabidopsis mesophyll protoplasts.
Binding of transcription factors to their target sequences is a primary step in the regulation of gene expression and largely determines gene regulatory networks. Chromatin immunoprecipitation (ChIP) is an indispensable tool used to investigate the binding of DNA-binding proteins (e.g., transcription factors) to their target sequences in vivo. ChIP assays require specific antibodies that recognize endogenous target transcription factors; however, in most cases, such specific antibodies are unavailable. To overcome this problem, many ChIP assays use transgenic plants that express epitope-tagged transcription factors and immunoprecipitate the protein with a tag-specific antibody. However, generating transgenic plants that stably express epitope-tagged proteins is difficult and time-consuming. Here, we present a rapid, efficient ChIP protocol using transient expression in Arabidopsis mesophyll protoplasts that can be completed in 4 days. We provide optimized experimental conditions, including the amount of transfected DNA and the number of protoplasts. We also show that the efficiency of our ChIP protocol using protoplasts is comparable to that obtained using transgenic Arabidopsis plants. We propose that our ChIP method can be used to analyze in vivo interactions between tissue-specific transcription factors and their target sequences, to test the effect of genotype on the binding of a transcription factor within a protein complex to its target sequences, and to measure temperature-dependent binding of a transcription factor to its target sequence. The rapid and simple nature of our ChIP assay using Arabidopsis mesophyll protoplasts facilitates the investigation of in vivo interactions between transcription factors and their target genes.


Cognitive vulnerability to depression in individuals with borderline personality disorder.
The goal of the current study was to examine whether individuals with comorbid Major Depressive Disorder (MDD) and Borderline Personality Disorder (BPD) exhibit greater severity of depressive symptoms than (1) individuals with MDD without BPD and (2) individuals with neither MDD nor BPD. One hundred and forty-one individuals participated in a semi-structured clinical interview assessing MDD and BPD. They also completed measures assessing depressive symptoms, depressogenic attributional style, hopelessness, self-esteem, rumination, and dysfunctional attitudes. In line with hypotheses, individuals with BPD and MDD exhibited higher levels of depressive symptoms and cognitive vulnerability than individuals in the other two groups. In addition, after controlling for the effects of cognitive vulnerability, the effect of group membership on depressive symptoms was reduced, suggesting that the increased severity of depressive symptoms experienced by those with BPD is partially due to their possessing higher levels of cognitive vulnerability to depression.


Thyroxine distribution and metabolism in familial dysalbuminemic hyperthyroxinemia.
We studied two families with familial dysalbuminemic hyperthyroxinemia (FDH), a recently described entity characterized by marked elevation of serum T4 due to increased binding of T4 to albumin. The seven affected subjects had elevated serum total T4 levels (range, 15.3-25.2 micrograms/dl; normal, 4.5-11.0 micrograms/dl), but normal serum free T4 levels, as measured by equilibrium dialysis. Their serum T3 levels ranged from 1.40-2.46 ng/ml (normal, 0.9-2.0 ng/ml). The proportion of T4 associated with serum albumin was increased approximately 4-fold in the affected subjects, as shown both by reverse flow paper electrophoresis and immunoprecipitation of albumin-bound T4 with antihuman serum albumin. In vivo T4 kinetic studies were performed in the two index subjects to assess the effects of the increased binding of T4 to albumin on the in vivo transport, distribution, and disposal of T4. Compared to values in normal subjects, the MCR of T4 was decreased by about 50%, and its total body (extrathyroidal) pool size was increased by approximately 50%; the T4 production rate was normal. The extracellular T4 pool size was increased by about 100% in the FDH subjects, but the rapidly exchangeable intracellular T4 pool size was normal. The unidirectional T4 clearance rate from plasma into the rapidly exchangeable cellular compartment was reduced by approximately 50%, but the absolute rate of T4 flux from plasma into the cellular compartment was normal. Thus, the in vivo kinetic data indicate that the increased plasma binding of T4 in FDH alters the distribution of T4 in favor of the extracellular compartment, retards the fractional rate of transfer of T4 into cells, and slows the metabolic clearance of T4. However, the absolute rate of T4 flux into the rapidly exchangeable cellular compartment, the intracellular T4 pool size, and the T4 disposal rate are all normal in FDH, consistent with the normal serum concentrations of free T4 and the eumetabolic state of these individuals.


[Acute urinary retention in a young woman with Lyme borreliosis].
Acute urinary retention (AUR) in females is a rare condition (annual incidence 3-7/100,000/year). In the past AUR was considered to be of psychogenic origin. Today diagnostic tools have improved and aetiologic factors for AUR are more easily diagnosed and managed. Causes of AUR can be of infectious, pharmacological, neurological, anatomical, myopathic and functional origin. We report a case of a woman aged 34 who presented with AUR caused by Lyme borreliosis. The patient fully recovered after intravenous antibiotic treatment and micturition returned to the habitual condition.


A theoretical study of isomerism in doped aluminum MAl12 and MAl12X12 clusters with 40 and 50 valence electrons.
Systematic density functional B3LYP calculations with the 6-31G* and 6-311+G* basis sets have been employed in order to investigate the structure, vibrational frequencies, relative energies, vertical ionization potentials, and magnetic shielding constants of endohedral and exohedral isomers in two related families of doped aluminum MAl12 and alane MAl12H12 clusters with 40 and 50 valence electrons, respectively. Isomerization barriers have been also determined. Trends in these properties with changing heteroatom M in various series have been followed. The similarities and differences between the aluminides and alanes as well as between the alanes MAl12H12 and related boranes MB12H12 and gallanes MGa12H12 have been scrutinized.


Ultrafast X-Ray Scattering Reveals Composite Amplitude Collective Mode in the Weyl Charge Density Wave Material (TaSe_{4})_{2}I.
We report ultrafast x-ray scattering experiments of the quasi-1D charge density wave (CDW) material (TaSe_{4})_{2}I following ultrafast infrared photoexcitation. From the time-dependent diffraction signal at the CDW sidebands we identify a 0.11 THz amplitude mode derived primarily from a transverse acoustic mode of the high-symmetry structure. From our measurements we determine that this mode interacts with the valence charge indirectly through another collective mode, and that the CDW system in (TaSe_{4})_{2}I has a composite nature supporting multiple dynamically active structural degrees of freedom.


Assisted Gestation and Transgender Women.
Developments in uterus transplant put assisted gestation within meaningful range of clinical success for women with uterine infertility who want to gestate children. Should this kind of transplantation prove routine and effective for those women, would there be any morally significant reason why men or transgender women should not be eligible for the same opportunity for gestation? Getting to the point of safe and effective uterus transplantation for those parties would require a focused line of research, over and above the study of uterus transplantation for non-transgender women. Some commentators object to the idea that the state has any duty to sponsor research of this kind. They would limit all publicly-funded fertility research to sex-typical ways of having children, which they construe as the basis of reproductive rights. This objection has no force against privately-funded research, of course, and in any case not all social expenditures are responses to 'rights' properly speaking. Another possible objection raised against gestation by transgender women is that it could alter the social meaning of sexed bodies. This line of argument fails, however, to substantiate a meaningful objection to gestation by transgender women because social meanings of sexed bodies do not remain constant and because the change in this case would not elicit social effects significant enough to justify closing off gestation to transgender women as a class.


A High-Fat Diet Rich in Saturated and Mono-Unsaturated Fatty Acids Induces Disturbance of Thyroid Lipid Profile and Hypothyroxinemia in Male Rats.
Increasing evidence has shown that the disturbance of lipid metabolism might make a possible contribution to the pathogenesis of organ dysfunction, including thyroid, yet it is unknown whether excess intake of dietary fat interferes in thyroid lipid profile. We investigate the effects of dietary fat toward the thyroid lipid profile and thyroid function. Male Sprague-Dawley rats are fed with high-fat diet (HFD) rich in saturated and mono-unsaturated fatty acids or chow diet for 18 weeks. LC-MS analysis of thyroid shows that total free fatty acids (FFAs) content is significantly higher in HFD rats. The concentration of highly saturated triglycerides significantly increases in HFD rats, whereas the polyunsaturated triglyceride significantly decreases, indicating the decrease in unsaturation in the HFD group. Significant increase of lysophosphatidylcholines (LPC) is observed in HFD rats. Thyroid function tests show hypothyroxinemia (total thyroxine [TT4 ] and free thyroxine [FT4 ]) in HFD rats, and elevated thyrotropin (TSH) concentration. The HFD rats also show decreased thyroid uptake of iodine. Excess intake of dietary fat induces disturbance of thyroid lipid profile and hypothyroxinemia, indicating thyroid dysfunction. We speculate that it may provide a new prospect in understanding the pathogenesis of hypothyroidism.


[Collagen structure and biomechanical properties of the goat temporomandibular joint disc].
To establish objectively biomechanical criteria for temporomandibular joint disc tissue engineerings. Eight temporomandibular joint discs from a four-month-old goat were separated completely. A cylindrical sample with diameter of 3 mm in the anterior, intermediate, and posterior bands was obtained, and the samples underwent pre-compression test with three cycles under a speed of 0.025 mm · s⁻¹. With the end condition for the maximum load of less than 4.9 N and 1.5 mm compression displacement, the formal compression test was performed with the same speed. Moreover, this test obtained the stress-strain relationship and elastic modulus of each disc band. Ultrastructure and collagen fiber orientation of the district zone were observed by scanning electron microscope and polarized light microscope. 1) The physiological strain range of an articular disc was within 10%, and the quasilinear constitutive equation of articular disc tissues can be fitted with the polynomial function: y = ax + bx² + cx³. 2) The elastic modulus of the intermediate disc zone was the largest (P < 0.05). No significant difference existed between the anterior and posterior bands (P = 0.361). 3) Scanning electron microscope and polarized light microscope showed an annular disc collagen network structure, which was the internal part of the goat temporomandibular joint disc. The collagen arrangement of intermediate bands was tensely arranged anterior-posteriorly. The collagen of anterior and posterior bands went through mediolaterally with intersection of anterior-posterior branch fibersd. Annular collagen network structure is the basis for goat temporomandibular joint disc compression resistance properties. The intermediate band demonstrated higher compression resistance performance than the anterior and posterior bands.


Primary integumentary xenograft reactivity in the American cockroach, Periplaneta americana.
The nature of cell-mediated immunity in the American cockroach (Periplaneta americana) was studied by observing the events involved in graft reactivity. Adult roaches received integumentary xenografts from Blaberus giganteus, as well as control autografts. Grafts were scored histologically by counting the number of nuclei in a 100-mu-wide area under the center of the graft. The data showed that the reaction to the xenografts was characterized by quick recognition of foreignness by day 3 posttransplantation, followed by a slow decline in the cellular response, which lasted for more than 70 days. Control autografts did not appear to stimulate a reaction. Histological examination of xenografts revealed a disruption of the normal cytoarchitecture by a heavy cellular infiltrate. Our findings indicate that the outcome of the response to foreign integument in the roach is more characteristic of an encapsulation reaction than a classic rejection reaction.


Effectiveness of a multidisciplinary education protocol in children with asthma (0-4 years) in primary health care.
This paper describes the results of an asthma self-management protocol delivered to parents of children aged 0-4 years. The protocol was delivered by general practitioners (GPs), community nurses, asthma nurses, and doctors to child health centers. It consisted of 16 educational modules developed after an initial needs assessment of parents and a task analysis of primary care practitioners. The program was evaluated by means of an experimental design. Parents participating in the program had significantly more knowledge, a more favorable attitude toward asthma, and a higher self-efficacy score with respect to performing asthma self-management behaviors. Also, they reported performing self-management behaviors more frequently than parents in the control group. One-year follow-up results, which were collected for parents in the treatment group only, showed that the described changes were sustained. Further, the treatment group was found to have decreased its emergency and nonemergency use of the physician's office and to have a reduction in (reported) asthma severity. Process evaluation indicated that most modules were provided by the GPs to nearly all parents. After parents had read the modules at home, almost all the information was discussed in the next contact. GPs seldom referred patients to the community nurses, although this was suggested in the protocol.


Psychiatric Disability in Law Enforcement Officers.
Law enforcement officers all across the world are exposed to violence, confrontation, and traumatic incidents. They regularly witness death and suffering and are at risk of personal injury. Psychiatric sequelae include an increased risk for trauma-related symptoms, depression, alcohol-use disorders, and stress-related medical conditions. Law enforcement officers have been applying for early disability retirement pensions at an increased rate for stress-related psychiatric and medical conditions. As a result, law enforcement agencies are prematurely losing valuable resources, officers with training and experience. Departments have become proactive in trying to address mental health issues to prevent psychiatric disability by implementing employee wellness plans and stress reduction interventions. Programs have been developed to mitigate the effects of stress on law enforcement personnel. Many law enforcement agencies have developed strategies to encourage early confidential referral for psychiatric treatment. They utilize peer support groups and employee assistance programs and develop alliances with mental health professionals. When these approaches fail, a fitness for duty process can be used to identify impairment in work functioning due to psychiatric factors with the prospect of later returning the officer to full duty. Copyright © 2017 John Wiley & Sons, Ltd.


First Reported Successful Femoral Valve-in-Valve Transcatheter Aortic Valve Replacement Using the Edwards Sapien 3 Valve.
Management of degenerated aortic valve bioprosthesis classically requires redo surgery, but transcatheter aortic valve-in-valve implantation is becoming a valid alternative in selected cases. In the case of a degenerated Mitroflow bioprosthesis, TAVR is associated with an additional challenge due to a specific risk of coronary occlusion. We aimed to assess the safety and feasibility of transfemoral valve-in-valve implantation of the new Edwards Sapien 3 (Edwards Lifesciences) in a degenerated Mitroflow bioprosthesis (Sorin Group, Inc). We report here the safety and feasibility of transfemoral valve-in-valve implantation of a 23 mm Edwards Sapien 3 in a degenerated 25 mm Mitroflow valve and describe the specific assessment of the risk of coronary obstruction using a multi-imaging modality. The final result showed an absence of aortic regurgitation and a mean transvalvular gradient of 14 mm Hg. The patient had no major adverse cardiovascular events at 30-day follow-up. Transcatheter valve-in-valve implantation of an Edwards Sapien 3 in a degenerated Mitroflow is feasible and safe, considering a careful assessment of the risk of coronary obstruction with Mitroflow bioprosthesis due to leaflets mounted externally to the stent.


Smooth and filamental structures in chaotically advected chemical fields.
This paper studies the spatial structure of decaying chemical fields generated by a chaotic-advection flow and maintained by a spatially smooth chemical source. Previous work showed that in a regime where diffusion can be neglected (large Péclet number), the structures are filamental or smooth depending on the relative strength of the chemical dynamics and the stirring induced by the flow. The scaling exponent, gamma(q), of the qth -order structure function depends, at leading order, linearly on the ratio of the rate of decay of the chemical processes, alpha , and the average rate of divergence of neighboring fluid parcel trajectories (Lyapunov exponent), h. Under a homogeneous stretching approximation, gamma(q)/q=max[alpha/h,1] which implies that a well-defined filamental-smooth transition occurs at alpha=h. This approximation has been improved by using the distribution of finite-time Lyapunov exponents to characterize the inhomogeneous stretching of the flow. However, previous work focused more on the behavior of the exponents as q varies and less on the effects of alpha and hence the implications for the filamental-smooth transition. Here we set out the precise relation between the stretching rate statistics and the scaling exponents and emphasize that the latter are determined by the distribution of the finite-size (rather than finite-time) Lyapunov exponents. We clarify the relation between the two distributions. We show that the corrected exponents, [symbol: see text] depend nonlinearly on alpha with [formula: see text]. The magnitude of the correction to the homogeneous stretching approximation, [formula: see text], grows as alpha increases, reaching a maximum when the leading-order transition is reached (alpha=h). The implication of these results is that there is no well-defined bulk filamental-smooth transition. Instead it is the case that the chemical field is unambiguously smooth for alpha>h(max), where h(max) denotes the maximum finite-time Lyapunov exponent and unambiguously filamental for alpha<h, with an intermediate character for alpha between these two values. Theoretical predictions are confirmed by numerical results obtained for a linearly decaying chemistry coupled to a renewing type of flow together with careful calculations of the Crámer function.


Regulation of CD4 T cells and their effects on immunopathological inflammation following viral infection.
CD4 T cells help immune responses, but knowledge of how memory CD4 T cells are regulated and how they regulate adaptive immune responses and induce immunopathology is limited. Using adoptive transfer of virus-specific CD4 T cells, we show that naive CD4 T cells undergo substantial expansion following infection, but can induce lethal T helper type 1-driven inflammation. In contrast, memory CD4 T cells exhibit a biased proliferation of T follicular helper cell subsets and were able to improve adaptive immune responses in the context of minimal tissue damage. Our analyses revealed that type I interferon regulates the expansion of primary CD4 T cells, but does not seem to play a critical role in regulating the expansion of secondary CD4 T cells. Strikingly, blockade of type I interferon abrogated lethal inflammation by primary CD4 T cells following viral infection, despite that this treatment increased the numbers of primary CD4 T-cell responses. Altogether, these data demonstrate important aspects of how primary and secondary CD4 T cells are regulated in vivo, and how they contribute to immune protection and immunopathology. These findings are important for rational vaccine design and for improving adoptive T-cell therapies against persistent antigens.


Novel HLA-DRB1 alleles discovered during routine sequencing based typing, DRB1*03052, DRB1*04032, DRB1*1139 and DRB1*1346.
We report the discovery of four HLA-DRB1 alleles during routine sequencing based typing (SBT). These alleles--DRB1*03052, DRB1*04032, DRB1*1139 and DRB1*1346--differ from previously identified DRB1 alleles by known nucleotide polymorphisms.


Production of Recombinant Human scFv Against Tetanus Toxin Heavy Chain by Phage Display Technology.
Tetanus, as a major cause of death in developing countries, is caused by tetanus neurotoxin. Recombinant antibodies against tetanus neurotoxin can be useful in tetanus management. Phage display of antibody fragments from immune human antibody libraries with single chain constructs combining the variable fragments (scFv) has been one of the most prominent technologies in antibody engineering. The aim of this study was the generation of a single chain fragment of variable region (scFv) library and selection of specific antibodies with high affinity against tetanus toxin. Immune human single chain fragment variable (HuscFv) antibody phagemid library was displayed on pIII of filamentous bacteriophage. Selection of scFv clones was performed against tetanus toxin antigens after three rounds of panning. The selected scFv clones were analyzed for inhibition of tetanus toxin binding to ganglioside GT1b. After the third round of panning, over 35 HuscFv phages specific for tetanus toxin were isolated from this library of which 15 clones were found to bind specifically to tetanus toxin. The selected HuscFv phages expressed as a soluble HuscFv peptide and some clones showed positive signals against tetanus toxin. We found that six HuscFv clones inhibit toxin binding to ganglioside GT1b. These selected antibodies can be used in the management of tetanus.


Increased frequency of metabolic syndrome and its individual metabolic abnormalities in Japanese patients with primary gout.
Gout patients are frequently complicated with hypertension, obesity, dyslipidemia, and/or impaired glucose tolerance, which are components of the metabolic syndrome and risks for atherosclerotic diseases. To determine the relationship between metabolic syndrome and gout, as well as plasma concentrations of adipocytokines in gout patients. The frequency of metabolic syndrome as well as its constituents were investigated in 258 male gout patients and 111 males who attended an annual check-up examination. In addition, plasma concentrations of adipocytokines were measured in 107 of the patients. Gout patients had a higher prevalence of metabolic syndrome as compared with the controls (36.4% vs. 15.3%, P < 0.0001). In addition, frequencies of individual metabolic abnormalities, such as waist circumference >85 cm, hypertension, and hypertriglyceridemia, were significantly increased in the gout patients as compared with the controls. Furthermore, uric acid over-production gout had a significantly higher prevalence of metabolic syndrome as compared with uric acid under-excretion gout (48.6% vs. 32.4%, P < 0.001). The plasma concentrations of leptin and plasminogen activator inhibitor-1 were significantly higher in the patients (P < 0.05, respectively), while that of adiponectin and the adiponectin/leptin ratio were significantly decreased in the gout patients as compared with the controls (P < 0.05, respectively). A higher prevalence of metabolic syndrome in gout patients may in part contribute to susceptibility to atherosclerotic diseases. Therefore, more attention should be paid to the presence of metabolic syndrome in gout patients to reduce their risk for cardiovascular disease complications.


Synthetic biology: lessons from engineering yeast MAPK signalling pathways.
All living cells respond to external stimuli and execute specific physiological responses through signal transduction pathways. Understanding the mechanisms controlling signalling pathways is important for diagnosing and treating diseases and for reprogramming cells with desired functions. Although many of the signalling components in the budding yeast Saccharomyces cerevisiae have been identified by genetic studies, many features concerning the dynamic control of pathway activity, cross-talk, cell-to-cell variability or robustness against perturbation are still incompletely understood. Comparing the behaviour of engineered and natural signalling pathways offers insight complementary to that achievable with standard genetic and molecular studies. Here, we review studies that aim at a deeper understanding of signalling design principles and generation of novel signalling properties by engineering the yeast mitogen-activated protein kinase (MAPK) pathways. The underlying approaches can be applied to other organisms including mammalian cells and offer opportunities for building synthetic pathways and functionalities useful in medicine and biotechnology.


[Four cases of pseudothrombocytopenia due to platelet cold agglutinins].
We report 4 cases of pseudothrombocytopenia due to platelet cold agglutinins. Case 1 was a 57 y.o. female whose platelet count was 97 x 10(3)/microl. Case 2 was a 37 y.o. male with a platelet count of 96 x 10(3)/microl. Case 3 was a 74 y.o. male with a platelet count of 28 x 10(3)/microl. Case 4 was a 62 y.o. female whose platelet count was 34 x 10(3)/microl. The platelet counts in these 4 cases were decreased and blood smears showed platelet clumping in blood drawn in a tube without anticoagulant just after withdrawal, as well as in blood drawn in a tube with anticoagulant. The platelets from these patients agglutinated at a temperature below 10 degrees C (case 1 and 4) and 24 degrees C (case 2). The immunoglobulin class of the platelet cold agglutinins in cases 1, 2 and 4 was IgM. Agglutinated platelets showed no activation marker, such as CD62P, CD63 or CD40L, on the surface of the platelets. The target antigen of cold agglutinins was GPIIb-IIIa in cases 1 and 2. We considered that the detection of platelet agglutination in blood without anticoagulant is important to diagnose pseudothrombocytopenia due to platelet cold agglutinins. Although this disease is considered to be very rare, we suspect that this disease may be misdiagnosed as pseudothrombocytopenia due to the presence of an anticoagulant, and overlooked.


Pharmacokinetic rationale for a malarial suppressant administered once monthly.
Serum was collected from six adults participating in a field trial of sulfadoxine and pyrimethamine in combination which was being administered once monthly for malaria suppression. Samples were drawn during each of two consecutive months three hours, and 7, 14 and 28 days following a dose of 1 500 mg sulfadoxine. Serum sulfadoxine concentration was measured using the method of Bratton and Marshall (1939). Initial serum concentrations averaged 19-9 plus or minus 2-4 (SD) mg/100 ml and decayed to 6-2 plus or minus 2-8 mg/100 ml at 14 days. Serum sulfadoxine concentrations were still detectable at 28 days following a dose (2-1 plus or minus 1-5 mg/100 ml). Elimination half-time averaged 195 plus or minus 44 hours. The presistent serum concentrations of sulfadoxine following monthly doses documented here during field-use of this drug are in agreement with the successful clinical results reported for such a regimen (Lewis and Ponnampalam, 1974; O'Holohan and Hugoe-Mathews, 1971; Wolfensberger, 1971).


Transient osteoporosis of hip joint with liver cirrhosis.
We describe the association between transient osteoporosis of the hip (TOH) and liver cirrhosis in a female patient. The clinical course, radiographic and scintigraphic features were similar to cases of TOH described previously. The pathogenesis of this syndrome is unknown and we suggest there may be a relationship between the hemodynamic changes common in cirrhotic patients and in pregnant women and the development of TOH.


Charge stabilization mechanism in the visual and purple membrane pigments.
The effects of charged groups of rhodopsin and bacteriorhodopsin on the potential energy surface of their chromophore are examined, taking into account the protein dielectric effect. It is found that the barriers for twisting double bonds of an isolated chromophore can be drastically reduced when the chromophore interacts with the protein charges. New types of local minima are found in the ground-state potential surface of the protein-chromophore complex. These minima correspond to "charge-stabilized intermediates" which are formed when a shift of the chromophore positive charge to the ring is stabilized by the ionization of a properly placed acidic group of the protein and by partial alternation of the bond lengths of the chromophore. It is suggested that the absorption of light by rhodopsin and bacteriorhodopsin may be used not only for isomerization about double bonds, but also for trapping such charge-stabilized intermediates. Thus, for example, it is concluded that prelumirhodopsin might be still in the cis configuration. Both the mechanism of the proton pump system of the purple membrane and the dark reaction of the visual and purple membrane pigments are considered. The connection between the finding of the present work and the mechanism of storage of light energy in photobiology is indicated.


rexAB mutants in Streptococcus pneumoniae.
Streptococcus pneumoniae is a human pathogen that is naturally transformable. In this study a major component of the homologous recombination pathway, the RexAB exonuclease/helicase, was characterized. rexA and rexB insertional mutants were constructed using mariner mutagenesis and found to have identical phenotypes. Both rexAB mutants displayed poor cell viability, reduced double-strand exonuclease activity, UV sensitivity and a reduced level of gene conversion compared to the wild-type strain. No effect was observed on plasmid and chromosomal transformation efficiencies. These results indicate that in S. pneumoniae, RexAB is required for DNA repair, but not for chromosomal transformation and plasmid establishment.


N400 amplitude does not recover from disappearance after repetitions despite reinitiated semantic integration difficulty.
It remains an open question whether the amplitude of N400 reflects combinatory postlexical semantic integration processing. To examine the issue, we repeatedly presented strictly simplified, N400-eliciting three-word structures for seven times, mixed with their plausible counterparts, followed immediately by a much more enriched and informative sentence containing two keywords of the incongruous structure, for the purpose of reinitiating semantic integration processing. Event-related potentials were recorded and compared at the first, fourth, seventh, and eighth time. It was found that multiple repetitions attenuated the N400 effect to almost nonexistent and that the follow-up semantic integration reinitiating sentence did not recover N400 amplitude. The results suggest that combinatory postlexical semantic integration does not significantly modulate N400 amplitude, and provide evidence for noncombinatory processes underlying N400 such as automatic spreading activation and expectancy/prediction.


Vaccination in Children With Autoimmune Disorders and Treated With Various Immunosuppressive Regimens: A Comprehensive Review and Practical Guide.
Children with autoimmune disorders are especially at risk of vaccine-preventable diseases due to their underlying disease and the immunosuppressive treatment often required for a long period. In addition, vaccine coverage remains too low in this vulnerable population. This can be explained by a fear of possible adverse effects of vaccines under immunosuppression, but also a lack of data and clear recommendations, particularly with regard to vaccination with live vaccines. In this review, the latest literature and recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to provide a set of practical guidelines on vaccination for specialists caring for children suffering from different autoimmune disorders and treated with various immunosuppressive regimens.


Effects of endurance training on alkaline protease activities in rat skeletal muscles.
This study aimed at comparing the effects of running and swimming training protocols and the termination of training on the activities of two proteases with alkaline pH-optima (alkaline protease and myofibrillar protease) in the tibialis anterior, soleus, and gastrocnemius muscles of male rats. The training on treadmill decreased the activities of alkaline and myofibrillar proteases by approx. 10-20% in the muscles studied. The activities of both proteases were unchanged in swimming-trained rats. Two weeks after the termination of running training the activity of alkaline protease was increased in gastrocnemius muscle but not in the other muscles. Swimming training increased the activity of citrate synthase in all muscles studied but training by running only in the soleus muscle. The running protocol increased the activity of beta-glucuronidase in the tibialis anterior muscle and decreased the activity in the gastrocnemius muscle. The swimming program did not affect beta-glucuronidase activities. These results show diverse effects of running and swimming training on alkaline proteolytic activities as well as on mitochondrial and lysosomal marker enzymes.


(2+1) resonance-enhanced ionization spectroscopy of a state-selected beam of OH radicals.
A state-selected beam of hydroxyl radicals is generated using a pulsed discharge source and hexapole field. The OH radicals are characterized by resonance-enhanced multiphoton ionization (REMPI) spectroscopy via the nested D 2Sigma- and 3 2Sigma- Rydberg states. Simplified spectra are observed from the selected |MJ|=3/2 component of the upper Lambda-doublet level of the lowest rotational state (J=32) in ground (v"=0) and excited (v"=1-3) vibrational levels of the OH X 2Pi3/2 state. Two-photon transitions are observed to the D 2Sigma-(v'=0-3) and 3 2Sigma-(v'=0,1) vibronic levels, extending previous studies to higher vibrational levels of the Rydberg states. Spectroscopic constants are derived for the Rydberg states and compared with prior experimental studies. Complementary first-principle theoretical studies of the properties of the D 2Sigma- and 3 2Sigma- Rydberg states [see M. P. J. van der Loo and G. C. Groenenboom, J. Chem. Phys. 123, 074310 (2005), following paper] are used to interpret the experimental findings and examine the utility of the (2+1) REMPI scheme for sensitive detection of OH radicals.


RNA Interference Screening Identifies Novel Roles for RhoBTB1 and RhoBTB3 in Membrane Trafficking Events in Mammalian Cells.
In the endomembrane system of mammalian cells, membrane traffic processes require a high degree of regulation in order to ensure their specificity. The range of molecules that participate in trafficking events is truly vast, and much attention to date has been given to the Rab family of small GTPases. However, in recent years, a role in membrane traffic for members of the Rho GTPase family, in particular Cdc42, has emerged. This prompted us to develop and apply an image-based high-content screen, initially focussing on the Golgi complex, using RNA interference to systematically perturb each of the 21 Rho family members and assess their importance to the overall organisation of this organelle. Analysis of our data revealed previously unreported roles for two atypical Rho family members, RhoBTB1 and RhoBTB3, in membrane traffic events. We find that depletion of RhoBTB3 affects the morphology of the Golgi complex and causes changes in the trafficking speeds of carriers operating at the interface of the Golgi and endoplasmic reticulum. In addition, RhoBTB3 was found to be present on these carriers. Depletion of RhoBTB1 was also found to cause a disturbance to the Golgi architecture, however, this phenotype seems to be linked to endocytosis and retrograde traffic pathways. RhoBTB1 was found to be associated with early endosomal intermediates, and changes in the levels of RhoBTB1 not only caused profound changes to the organisation and distribution of endosomes and lysosomes, but also resulted in defects in the delivery of two different classes of cargo molecules to downstream compartments. Together, our data reveal new roles for these atypical Rho family members in the endomembrane system.


Retinal Detachments in Pediatric Patients With X-Linked Retinoschisis: Characteristics and Surgical Outcomes.
Retinal detachments (RDs) are a complication of X-linked retinoschisis (XLRS) with a poor prognosis. This study aims to report outcomes of XLRS-RD repair in pediatric patients. The study is a retrospective analysis of pediatric patients undergoing vitreoretinal surgery for XLRS-RDs from 2000 to 2022. Nine patients (11 eyes) met inclusion criteria. All patients were boys, with a mean age of 8 years. Most RDs arose inferiorly (64%). Seven (64%) detachments were macula-involving. Seven (64%) detachments were repaired with combined scleral buckling and vitrectomy, two (18%) detachments were repaired with vitrectomy alone, one (9%) detachment underwent a primary scleral buckling procedure, and one (9%) asymptomatic detachment with a pigment demarcation line was observed. Silicone oil was used in eight of nine (89%) eyes undergoing vitrectomy. Final visual acuity was 20/200 or better in eight (73%) eyes. One eye that underwent surgical intervention remained unattached at follow-up. Surgical repair in patients with XLRSRDs was associated with successful reattachment, although visual prognosis varied. [Ophthalmic Surg Lasers Imaging Retina 2023;54:574-579.].


The R-factors of multiple antibiotic resistant faecal coliforms isolated from a domestic dog.
The antibiotic resistant faecal flora of a domestic dog suffering from an acute enteric infection was examined. The flora exhibited overall resistance to a wide variety of antibiotics. However, following restoration of the animal to normal health, overall resistance to ampicillin (Ap), tetracycline (Tc), chloramphenicol (Cm) and streptomycin Sm was lost, although low numbers of bacteria resistant to these four antimicrobial agents could still be isolated up to one year later. A total of 11 strains were purified for further study. All 11 were positively identified as Escherichia coli and shown to be resistant to various combinations of the above antibiotics, and additionally to kanamycin (Km). Each strain harboured from one to five plasmids, although only four proved capable of transferring antibiotic resistance to Escherichia coli K-12. One of the strains was found to harbour two conjugal plasmids pNJ101 (60 Md) and pNJ102 (133 Md) which coded for resistance to Cm, Tc, Ap and Cm, Tc, Km respectively. A third plasmid pNJ103 (29 Md) remains cryptic. The possession of the two plasmids pNJ101 and pNJ102 appears to be an unstable situation as variants arose harbouring one or other of the plasmids.


Adult disclosure of a history of childhood sexual abuse: implications for behavioral psychotherapy.
This article presents a behavioral conceptualization of the difficulties associated with adult disclosure in psychotherapy of a history of childhood sexual abuse. Using a contemporary behavioral perspective and a functional analysis of various clinical presentations, we examine the factors that may contribute to nondisclosure of a history of abuse. Traumagenic dynamics are used to frame a discussion of childhood factors that may further influence disclosure of abuse. The construct of stigma is linked to aspects of experiential avoidance, which is considered to be a core mediator of the difficulties associated with a history of abuse. Acceptance and commitment therapy and functional analytic psychotherapy, 2 "third-wave" behavioral treatments, are presented generally with specific discussions of these therapies as they relate to the issue of disclosure. Important therapist factors as well as implications for future investigations are presented.


Comparison of the Fungistatic Activity of Selected Essential Oils Relative to Fusarium graminearum Isolates.
The aim of the study was to determine the chemical composition of lemon, rosewood, geranium and rosemary oils, and compare their effect on the sensitivity of Fusarium graminearum ZALF 24 and Fusarium graminearum ZALF 339 isolated from infected cereals. The tested oils were added to Potato Dextrose Agar (PDA) medium at concentrations of 0.125%, 0.25%, 0.5%, 1.0% and 2.0%. The activity of the oils on inhibition of the linear growth of mycelium was evaluated by measuring the growth of fungal colonies (growth index), while the fungistatic activity was evaluated on the basis of the percentage growth inhibition of a fungal colony and calculated according to Abbott's formula. The sensitivity of the test strains was variable and depended on the type and concentration of the tested oils. Geranium and rosewood oils in all of the concentrations completely inhibited the growth of the used isolates. In contrast, lemon oil relative to F. graminearum ZALF 339 showed the highest activity at a concentration of 1.0% and rosemary oil, 0.5%. The highest activity against F. graminearum ZALF 24 was shown by the oils of rosemary and lemon at concentrations from 1.0% to 2.0%. The susceptibility of Fusarium graminearum isolates was differentiated and depended on the type and concentration of tested oils.


Health sciences librarians' attitudes toward the Academy of Health Information Professionals.
The purpose of the study was to ascertain health sciences librarians' attitudes toward the Academy of Health Information Professionals (AHIP). Systematic sampling was used to select 210 names from the list of members of the Midwest Chapter of the Medical Library Association. A questionnaire containing open- and closed-ended questions was used to collect the data. A total of 135 usable questionnaires were returned. Of the respondents, 34.8% are members of the academy and most are at the senior or distinguished member levels. The academy gives them a sense of professionalism and helps them to keep current with new trends. The majority of participants (65.2%) are not members of the academy. Among the various reasons proffered are that neither institutions nor employers require it and that there is no obvious benefit to belonging to the academy. More research needs to be done with a larger sample size to determine the attitudes of health sciences librarians, nationwide, toward the academy.


Wheel running, voluntary ethanol consumption, and hedonic substitution.
Few studies have examined the relationship between naturally rewarding behaviors and ethanol drinking behaviors in mice. Although natural and drug reinforcers activate similar brain circuitry, there is behavioral evidence suggesting food and drug rewards differ in perceived value. The primary goal of the present study was to investigate the relationships between naturally reinforcing stimuli and consumption of ethanol in ethanol preferring C57BL/6J mice. Mouse behaviors were observed after the following environmental manipulations: standard or enhanced environment, accessible or inaccessible wheel, and presence or absence of ethanol. Using a high-resolution volumetric drinking monitor and wheel running monitor, we evaluated whether alternating access to wheel running modified ethanol-related behaviors and whether alternating access to ethanol modified wheel running or subsequent ethanol-related behaviors. We found that ethanol consumption remains stable with alternating periods of wheel running. Wheel running increases in the absence of ethanol and decreases upon reintroduction of ethanol. Upon reintroduction of ethanol, an alcohol deprivation effect was seen. Collectively, the results support theories of hedonic substitution and suggest that female C57BL/6J mice express ethanol seeking and craving under these specific conditions.


[Denervation supersensitivity of the detrusor muscle due to prolonged bladder overdistension].
The influence of prolonged bladder overdistension on the detrusor muscle was studied in female mongrel dogs. Two overdistending methods were employed, namely, constantly elevated hydrostatic pressure for one hour and bladder neck ligation for 48 hours. The cystometrogram and urinalysis at 2 weeks after release of overdistension were compared with the preoperative estimations. Using the in vitro isometric technique, the contractility of the detrusor muscle strip to acetylcholine was evaluated in the untreated control group and the two overdistended groups. Prolonged bladder overdistension for one hour as well as 48 hours resulted in a high incidence of urinary tract infection. There was no correlation between the cystometric findings before and after overdistension . An increase in contraction response to acetylcholine was observed in both overdistended groups. Besides, a small contraction response to acetylcholine at a lower concentration was observed in the group overdistended for 48 hours. It is suggested that the observed contraction response increase was probably due to axonal degeneration caused by a decrease in the blood supply to the overdistended bladder wall.


Factors Associated with Suicide and Bankruptcy in Japanese Pathological Gamblers.
Pathological gambling can lead to a number of deleterious consequences, including bankruptcy and suicide. The present study examined the correlation between clinical characteristics of pathological gamblers and history of bankruptcy and suicide attempts. Subjects (141; 124 male) were outpatients at a psychiatric hospital from 2007 to 2010. Demographic and medical variables including age, gender, age of gambling onset, psychiatric complications, suicide attempts, and bankruptcy were assessed. Positive correlations were observed between suicide attempt and female gender, family history of addiction, and unemployment (p < 0.05). Similar variables correlated with bankruptcy (p < 0.05). Multivariate analysis revealed that a family history of addiction was the strongest independent predictor of suicide and bankruptcy. Results suggest that treatment for pathological gambling should address the patient's past experience with addict family members, especially if the patient reports a history of bankruptcy or suicidal ideation.


Role of trimer-trimer interaction of bacteriorhodopsin studied by optical spectroscopy and high-speed atomic force microscopy.
Bacteriorhodopsin (bR) trimers form a two-dimensional hexagonal lattice in the purple membrane of Halobacterium salinarum. However, the physiological significance of forming the lattice has long been elusive. Here, we study this issue by comparing properties of assembled and non-assembled bR trimers using directed mutagenesis, high-speed atomic force microscopy (HS-AFM), optical spectroscopy, and a proton pumping assay. First, we show that the bonds formed between W12 and F135 amino acid residues are responsible for trimer-trimer association that leads to lattice assembly; the lattice is completely disrupted in both W12I and F135I mutants. HS-AFM imaging reveals that both crystallized D96N and non-crystallized D96N/W12I mutants undergo a large conformational change (i.e., outward E-F loop displacement) upon light-activation. However, lattice disruption significantly reduces the rate of conformational change under continuous light illumination. Nevertheless, the quantum yield of M-state formation, measured by low-temperature UV-visible spectroscopy, and proton pumping efficiency are unaffected by lattice disruption. From these results, we conclude that trimer-trimer association plays essential roles in providing bound retinal with an appropriate environment to maintain its full photo-reactivity and in maintaining the natural photo-reaction pathway.


Identification of potential clinically significant drug interactions in HIV-infected patients: a comprehensive therapeutic approach.
The aim of the study was to determine the prevalence of potential clinically significant drug interactions (CSDIs) in HIV-positive individuals and to identify associated risk factors. A cross-sectional study was conducted including all HIV-infected out-patients attending the Pharmacy Service of a regional reference hospital in Murcia, south-eastern Spain. The complete treatment was screened for possible CSDIs using the Spanish College of Pharmacists' online software resource, bot. Additionally, the severity level of the CSDIs involving antiretroviral (ARV) drugs was compared with that established in the specific antiretroviral database InteraccionesHIV.com. Multivariate logistic regression was used to identify associated risk factors. Two hundred and sixty-eight patients were included in the study. A total of 292 potential drug interactions were identified, of which 102 (34.9%) were CSDIs, of which 52.9% involved ARV drugs. Seven therapeutic drug classes were involved in 75% of CSDIs (protease inhibitors, benzodiazepines, nonsteroidal anti-inflammatory drugs, nonnucleoside reverse transcriptase inhibitors, corticosteroids, antithrombotics and proton pump inhibitors). Factors independently associated with CSDIs were treatment with more than five drugs [odds ratio (OR) 15.1; 95% confidence interval (CI) 6.3-36.2], and treatment with a protease inhibitor (OR 5.3; 95% CI 2.4-11.74). The findings of this study suggest that the prevalence of clinically relevant drug-drug interactions is high in HIV-infected patients, and could represent a major health problem. Awareness, recognition and management of drug interactions are important in optimizing the pharmaceutical care of HIV-infected patients and helping to prevent adverse events and/or loss of efficacy of the drugs administered.


Tailoring 3D Speckle Statistics.
We experimentally generate three-dimensional speckles with customized intensity statistics. By appropriately modulating the phase front of a laser beam, the far-field speckles can maintain a desired intensity probability density function upon axial propagation: while evolving into different spatial patterns. We also demonstrate how to design speckle patterns that obtain distinct tailored intensity statistics on multiple designated axial planes. The ability to design 3D speckle statistics opens many possibilities: three-dimensional imaging and sensing, optical trapping, and manipulation.


Validation of physical activity measurement for people on dialysis treatment.
Chronic illness frequently contributes to diminished levels of activity, a consequent increased dependence on health related support services and reduced quality of life. Surprisingly few studies have described activity among people with end-stage renal disease (ESRD). The current study examined the utility and validity of the Human Activity Profile (HAP) for describing activity in a sample of Australians with ESRD. A descriptive design supported the primary objective of validating the use of HAP for an Australian renal population. Data was collected from 65 adults with ESRD under the care of one regional and one metropolitan renal unit in Victoria. The HAP measures physical activity across a range of activities of daily living, including a dyspnoea scale. The Sickness Impact Profile (SIP) describes activities associated with daily living in the areas of physical, psychological and independence. The HAP, SIP and a questionnaire summarising demographic and diagnostic details were administered while each person was undergoing dialysis and the results subsequently compared. This study demonstrates that HAP is a valid measure of activity levels for people with ESRD undergoing maintenance haemodialysis. Additionally, scores on SIP and HAP indicate that this group have low levels of daily activity. These findings support the use of HAP in research to understand the activity levels of ESRD patients and the factors associated with decline.


From single atoms to self-assembled quantum single-atomic nanowires: noble metal atoms on black phosphorene monolayers.
Transition metal (TM) nanostructures, such as one dimensional (1D) nanowires with/without substrates, usually possess drastically different properties from their bulk counterparts, due to their distinct stacking and electronic confinement. Correspondingly, it is of great importance to establish the dominant driving force in forming 1D single-metal-atom-wires (SMAWs). Here, with first-principles calculations, taking the black phosphorene (BP) monolayer as a prototype 2D substrate, we investigate the energetic and kinetic properties of all the 5d-TM atoms on the 2D substrate to reveal the mechanism of formation of SMAWs. In contrast to other 5d- and 4d-TMs, noble metal elements Pd and Pt are found to prefer to grow along the trough in an atom-by-atom manner, self-assembling into SMAWs with a significant magic growth behavior. This is due to distinct binding energies and diffusion barriers along the trough, i.e., zig-zag direction, as compared to other directions of the BP. The present findings are valuable in the fabrication and modulation of 1D nanostructures which can be anticipated to possess desirable functionalities for potential applications such as in nanocatalysis, nanosensors, and related areas.


[Subjective misconcepts of social status and coronary troubles (author's transl)].
The study of various social parameters as risk factors for coronary diseases gives contradictory results. The inadequacy of social status and the consequent subjective misconcept could reconcile these apparent oppositions. The present research seems to confirm the fact that misconcepts induced by inadequacity of social status are more frequent and more intensive in patients with coronary troubles.


Neurological abnormalities in familial and sporadic schizophrenia.
Neurological assessment was carried out on patients with schizophrenia from multiply and singly affected families, their relatives, and a normal control group (214 subjects). A systematic examination was used in which abnormal signs were divided into 'primary' and 'integrative' signs. Primary signs were elicited by a standard clinical neurological examination and included signs of focal damage to nuclei and tracts, whilst integrative signs were selected as reflecting distributed brain function. The assessments were carried out to test the hypotheses that (i) neurological abnormalities are present in schizophrenia, (ii) the pattern of abnormality is different in familial and sporadic schizophrenic subjects, and (iii) the well relatives of familial (but not sporadic) schizophrenic subjects will show neurological abnormalities. An excess of primary signs compared with the controls was demonstrated in the sporadic schizophrenic group only. Both the familial schizophrenics and their first-degree relatives (but not their sporadic counterparts) showed an increase in integrative signs. The results support the existence of different mechanisms of underlying brain dysfunction in familial and sporadic schizophrenia.


Risk factors for coronary artery disease in patients with elevated high-density lipoprotein cholesterol.
High high-density lipoprotein (HDL) levels protect against coronary artery disease (CAD) development. We hypothesized that patients with CAD and high HDL levels would have higher prevalence of other CAD risk factors compared with patients with CAD and normal HDL. We identified 41,982 patients from a single center with normal levels (40 to 60 mg/dl in men, 50 to 70 mg/dl in women) or high HDL levels (> or =70 mg/dl in men, > or =80 mg/dl in women) when last measured between January 2000 and April 2004. From this overall population, we characterized a cohort of 1,610 patients with CAD, including 98 patients with high HDL levels. We measured prevalence of traditional CAD risk factors by comparing these 98 patients with patients with CAD and normal HDL levels (n = 1,512). We performed manual chart review in patients (n = 196) matched 1:1 by age, gender, and HDL level to obtain further detail with regard to differences in family history and lifestyle factors. In patients with CAD, those with high HDL levels (98 of 1,610, 6.1%) were of similar age (71.1 vs 69.6 years, p = 0.23), had similar prevalence of hypertension (78.6% vs 88.7%, p = 0.30), lower levels of low-density lipoprotein (85.3 vs 90.9 mg/dl, p = 0.04) and triglycerides (87.1 vs 141.2 mg/dl, p <0.01), and a lower prevalence of diabetes (28.6% vs 38.4%, p = 0.05) compared with patients with normal HDL levels. In logistic regression models, patients with high HDL levels and CAD were less likely to have diabetes (adjusted odds ratio 0.60, 95% confidence interval 0.38 to 0.95, p = 0.03) or obesity (adjusted odds ratio 0.50, 95% confidence interval 0.25 to 0.99, p = 0.046) than patients with normal HDL levels and CAD. In conclusion, patients with high HDL and CAD had a similar or lower prevalence of traditional CAD risk factors compared with patients with normal HDL levels and CAD.


PRMT1 and PRMT5: on the road of homologous recombination and non-homologous end joining.
DNA double-strand breaks (DSBs) are widely accepted to be the most deleterious form of DNA lesions that pose a severe threat to genome integrity. Two predominant pathways are responsible for repair of DSBs, homologous recombination (HR) and non-homologous end-joining (NHEJ). HR relies on a template to faithfully repair breaks, while NHEJ is a template-independent and error-prone repair mechanism. Multiple layers of regulation have been documented to dictate the balance between HR and NHEJ, such as cell cycle and post-translational modifications (PTMs). Arginine methylation is one of the most common PTMs, which is catalyzed by protein arginine methyltransferases (PRMTs). PRMT1 and PRMT5 are the predominate PRMTs that promote asymmetric dimethylarginine and symmetric dimethylarginine, respectively. They have emerged to be crucial regulators of DNA damage repair. In this review, we summarize current understanding and unaddressed questions of PRMT1 and PRMT5 in regulation of HR and NHEJ, providing insights into their roles in DSB repair pathway choice and the potential of targeting them for cancer therapy.


Cationic lipid is not required for uptake and selective inhibitory activity of ICAM-1 phosphorothioate antisense oligonucleotides in keratinocytes.
Keratinocyte intercellular adhesion molecule-1 (ICAM-1) is important in mediating retention of T cells within the epidermal compartment. To determine if antisense oligonucleotides designed to hybridize to various ICAM-1 mRNA regions could selectively influence cultured keratinocyte ICAM-1 expression following gamma interferon (IFN-gamma), cells were exposed to several antisense compounds, in the absence and presence of cationic lipid (lipofectin). Keratinocytes rapidly internalized sense and antisense compounds (within 30-60 min), even in the absence of lipofectin with approximately 30% of the cell possessing positive nuclei. Such nuclear accumulation was not observed in the absence of lipofectin in cultured fibroblasts, smooth muscle cells, or endothelial cells, even though total cellular uptake within the cytoplasm was significantly increased in all these cell types. Using flow cytometry, IFN-gamma-inducible ICAM-1 expression was reduced 50% by antisense compounds with lipofectin, and by 30% without lipofectin. This inhibition was specific as no change was observed for HLA-DR or tumor necrosis factor-alpha receptor expression. Northern blot hybridization studies confirmed that ICAM-1 antisense oligonucleotides selectively and significantly inhibited ICAM-1 expression. These results suggest that such antisense compounds interact with keratinocytes differently than other cell types, and provide the in vitro basis for clinical trials in which reduction (or elimination) of ICAM-1 expression by epidermal keratinocytes could be selectively accomplished without necessarily influencing dermal cell types such as fibroblasts, endothelial cells, or smooth muscle cells.


Effects of some cryopreservation procedures on recalcitrant zygotic embryos of Ammocharis coranica.
Cryopreservation, the most promising method for the long-term conservation of recalcitrant (desiccation-sensitive) seed germplasm, is often associated with high viability losses. Cryo-procedures involve a sequence of steps which must be optimised to reduce the impact of the stresses. This study reports on the effects of some of the steps of cryopreservation on the recalcitrant zygotic embryos of the amaryllid, Ammocharis coranica. Embryos were subjected to cryoprotection with glycerol and/or DMSO, rapid (flash) drying, and rapid (>100 degree C s(-1)) or slow (1 degree C s(-1)) cooling. Rapid dehydration (from c. 2.7 to 0.9 g g(-1) over 60 min) and cooling had a detrimental effect on the viability of the embryos, which was exacerbated when these steps were applied sequentially. After cooling, seedling production (30%) was obtained only from embryos that had been cryoprotected with glycerol prior to drying and rapid cooling, while 30% of non-treated embryos and 70% of those that had undergone cathodic protection during flash drying produced callus. Noting that no post-cryo survival of A. coranica embryos had previously been obtained, this study identified cryoprotection with glycerol and the incorporation of cathodic protection during flash drying as promising intervention points for future studies.


Cycles, randomness, and transport from chaotic dynamics to stochastic processes.
An overview of advances at the frontier between dynamical systems theory and nonequilibrium statistical mechanics is given. Sensitivity to initial conditions is a mechanism at the origin of dynamical randomness-alias temporal disorder-in deterministic dynamical systems. In spatially extended systems, sustaining transport processes, such as diffusion, relationships can be established between the characteristic quantities of dynamical chaos and the transport coefficients, bringing new insight into the second law of thermodynamics. With methods from dynamical systems theory, the microscopic time-reversal symmetry can be shown to be broken at the statistical level of description in nonequilibrium systems. In this way, the thermodynamic entropy production turns out to be related to temporal disorder and its time asymmetry away from equilibrium.


Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment.
Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320-400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280-320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of CMM and describe an unexpected and significant role for melanin within the melanocyte in melanomagenesis.


High-Performance MoC Electrocatalyst for Hydrogen Evolution Reaction Enabled by Surface Sulfur Substitution.
Molybdenum carbides have been expected to be one of the promising catalysts for the hydrogen evolution reaction (HER) due to their similar d-band electronic structures to the Pt-group metals. However, the weaker hydrogen-adsorption ability of MoC severely hinders its applications. Guided by density functional theory calculations, we put forward a strategy to design the novel MoC-based electrocatalyst with surface reconstruction through sulfur doping. The incorporation of minor sulfur not only greatly increases the number of active sites and intrinsic activity but also optimizes the electronic structure to improve the electron transfer efficiency. As a result, the as-prepared sulfur-substituted MoC tackles the limitation of the Volmer step and exhibits superior HER performance with a small Tafel slope of 48 mV dec-1. Theoretical investigations demonstrate that the terminal sulfur plays a critical role in facilitating a close to zero hydrogen adsorption energy (ΔGH*) and a lower hydrogen release barrier.


Monitoring aerobic capacity in cancer survivors using self-reported questionnaires: criterion validity and responsiveness.
Evaluating the criterion validity and responsiveness of the self-reported FitMáx©-questionnaire, Duke Activity Status Index (DASI) and Veterans Specific Activity Questionnaire (VSAQ) to monitor aerobic capacity in cancer survivors. Cancer survivors participating in a 10-week supervised exercise program were included. The FitMáx©-questionnaire, DASI, VSAQ and a cardiopulmonary exercise test (CPET) were completed before (T0) and after (T1) the program. Intraclass correlation coefficients (ICC) were calculated between VO2peak estimated by the questionnaires (questionnaire-VO2peak) and VO2peak measured during CPET (CPET-VO2peak), at T0 to examine criterion validity, and between changes in questionnaire-VO2peak and CPET-VO2peak (ΔT0-T1) to determine responsiveness. Receiver operating characteristic (ROC) analyses were performed to examine the ability of the questionnaires to detect true improvements (≥ 6%) in CPET-VO2peak. Seventy participants were included. Outcomes at T1 were available for 58 participants (83%). Mean CPET-VO2peak significantly improved at T1 (Δ1.6 mL·kg- 1·min- 1 or 8%). Agreement between questionnaire-VO2peak and CPET-VO2peak at T0 was moderate for the FitMáx©-questionnaire (ICC = 0.69) and VSAQ (ICC = 0.53), and poor for DASI (ICC = 0.36). Poor agreement was found between ΔCPET-VO2peak and Δquestionnaire-VO2peak for all questionnaires (ICC 0.43, 0.19 and 0.18 for the FitMáx©-questionnaire, VSAQ and DASI, respectively). ROC analysis showed that the FitMáx©-questionnaire was able to detect improvements in CPET-VO2peak (area under the curve, AUC = 0.77), when using a cut-off value of 1.0 mL·kg- 1·min- 1, while VSAQ (AUC = 0.66) and DASI (AUC = 0.64) could not. The self-reported FitMáx©-questionnaire has sufficient validity to estimate aerobic capacity in cancer survivors at group level. The responsiveness of the FitMáx©-questionnaire for absolute change is limited, but the questionnaire is able to detect whether aerobic capacity improved. The FitMáx©-questionnaire showed substantial better values of validity and responsiveness compared to DASI and VSAQ.


Large scale use of Spherosil ion exchangers in plasma fractionation.
Spherosil microbeads are spherical and made of porous silica. Their surface is coated with hydrophilic and/or hydrophobic polymers. They are specially designed for the separation of proteins on an industrial scale either by ion exchange or by bioaffinity chromatography. Since 1980, large columns have been used in Institut Mérieux for the purification of placental albumin and several vaccines. Here we describe a chromatographic process for the purification of human albumin and immunoglobulins (IgG) from 25 1 of plasma per cycle. First the plasma was freed of the coagulation factors and then clarified at pH 5.25. The corresponding supernatant was filtered and processed in sterile conditions. Albumin was then purified by ion exchange on 3 successive columns, respectively containing: 6.25 kg of DEAE SPHEROSIL W-1000; 3.5 kg of QMA SPHEROSIL PH-1000; 8 kg of COOH-SPHEROSIL W-1000. The concentration and pH of the buffers were selected to reduce, as much as possible, the total quantity of ion exchangers required per cycle. IgG were then purified from the filtrate of the first of the previous columns. 1 column of 6.25 kg of DEAE SPHEROSIL W-1000 was used at pH 6.8. The selected chromatographic parameters allowed us to demonstrate a total elimination of HBs Ag and HB Virus when voluntarily added to an initial sample (RIA determination and HBV-DNA analysis by molecular hybridization). A second column of a large pore anion exchanger: DEAE SPHEROSIL LP-3000 was added at the end of the IgG purification, as a final security to avoid any risk of transmitting the Hepatitis B virus. The yield and quality of the final products will be presented.


A salty cause of severe hypertension.
A 51-year-old lady was referred to our clinic because of severe hypertension; blood pressure 214/119 mm Hg despite treatment with an angiotensin receptor antagonist and a calcium channel blocker. Her initial laboratory results showed hypokalaemic alkalosis with normal urea and creatinine levels. Her 24-h urinary sodium excretion was markedly elevated at 244 mmol (equivalent to a daily intake of approximately 16 g of salt). Hyperaldosteronism was suspected but her plasma aldosterone level was subsequently found to be normal. On further questioning, the patient admitted to eating considerable amounts of salted liquorice and a diagnosis of acquired apparent mineralocorticoid excess was made. Liquorice has a well-known mineralocorticoid activity as it inhibits the action of 11β-hydroxysteroid dehydrogenase 2 and can induce mineralocorticoid hypertension. After stopping eating the salted liquorice, the patient's blood pressure quickly normalised and all her antihypertensive medications were stopped.


People are variables too: multilevel structural equations modeling.
The article uses confirmatory factor analysis (CFA) as a template to explain didactically multilevel structural equation models (ML-SEM) and to demonstrate the equivalence of general mixed-effects models and ML-SEM. An intuitively appealing graphical representation of complex ML-SEMs is introduced that succinctly describes the underlying model and its assumptions. The use of definition variables (i.e., observed variables used to fix model parameters to individual specific data values) is extended to the case of ML-SEMs for clustered data with random slopes. Empirical examples of multilevel CFA and ML-SEM with random slopes are provided along with scripts for fitting such models in SAS Proc Mixed, Mplus, and Mx. Methodological issues regarding estimation of complex ML-SEMs and the evaluation of model fit are discussed. Further potential applications of ML-SEMs are explored.


Simultaneous activation and inhibition of autophagy sensitizes cancer cells to chemotherapy.
While combined chemotherapy (CT) with an autophagy inducer and an autophagy inhibitor appears paradoxical, it may provide a more effective perturbation of autophagy pathways. We used two dissimilar cell lines to test the hypothesis that autophagy is the common denominator of cell fate after CT. HA22T cells are characterized by CT-induced apoptosis and use autophagy to prevent cell death, while Huh7.5.1 cells exhibit sustained autophagic morphology after CT. Combined CT and rapamycin treatment resulted in a better combination index (CI) in Huh7.5.1 cells than combined CT and chloroquine, while the reverse was true in HA22T cells. The combination of 3 drugs (triplet drug treatment) had the best CI. After triplet drug treatment, HA22T cells switched from protective autophagy to mitochondrial membrane permeabilization and endoplasmic reticulum stress response-induced apoptosis, while Huh7.5.1 cells intensified autophagic lethality. Most importantly, both cell lines showed activation of Akt after CT, while the triplet combination blocked Akt activation through inhibition of phospholipid lipase D activity. This novel finding warrants further investigation as a broad chemosensitization strategy.


Highly Sensitive Artificial Skin Perception Enabled by a Bio-inspired Interface.
Piezoionic strain sensors have attracted enormous attention in artificial skin perception because of high sensitivity, lightweight, and flexibility. However, their sensing properties are limited by a weak material interface based on physical adhesion, which usually leads to fast performance deterioration under mechanical conditions. In this work, a bio-inspired interface has been reported based on an in situ growth strategy and then utilized for piezoionic sensor assembly. The robust coupling interface provides fast kinetic of ion transfer and prevents interface slippage under external strains. The as-fabricated sensors give high sensing voltage with high sensitivity. It delivers excellent cycling stability with performance retention above 90% over thousands of bending cycles in air. Further, the sensors have been explored as an effective platform for skin perception, and many detections can be realized within our devices, such as skin touch, eye movement, cheek bulging, and finger movement.


Spontaneous symmetry breaking by charge stripes in the high pressure phase of superconducting La1.875Ba0.125CuO4.
In those cases where charge-stripe order has been observed in cuprates, the crystal structure is such that the average rotational symmetry of the CuO2 planes is reduced from fourfold to twofold. As a result, one could argue that the reduced lattice symmetry is essential to the existence of stripe order. We use pressure to restore the average fourfold symmetry in a single crystal of La1.875Ba0.125CuO4, and show by x-ray diffraction that charge-stripe order still occurs. Thus, electronically driven stripe order can spontaneously break the lattice symmetry.


Clinical profile and predictors of therapeutic outcome with azithromycin in pediatric scrub typhus: A study from Eastern India.
In this prospective study, children from 1-month to 12-years, admitted with positive IgM ELISA testing for scrub typhus, were enrolled over 1-year and administered an empirical single dose of azithromycin (10 mg/kg). All 189 (median age 4.84-years) children had fever with median duration of 8 days at admission. Shortness of breath, altered sensorium, headache, lymphadenopathy, hepatosplenomegaly, pallor, oedema and hypotension were the most prominent symptoms/signs. About 46% of children developed complications, among them hepatic, neurological and cardiovascular were most common. Our study showed a remarkable response to azithromycin, with mean defervescence of 32 h and no mortality. The presence of shortness of breath, headache, altered sensorium, hepatosplenomegaly, meningeal signs, severe anemia, leucocytosis, hyponatremia along with/without any of above mentioned three systemic complications were independent predictors for delayed treatment response by multivariate logistic regression analysis. Hepatic, neurological and cardiovascular complications are an emerging trend. Empiric azithromycin based on clinical suspicion of scrub typhus can be lifesaving.


Nanoparticle-mediated monitoring of carbohydrate-lectin interactions using Transient Magnetic Birefringence.
The development of sensitive and easy-to-use biosensors that allow an adequate characterization of specific weak biological interactions like carbohydrate-lectin interactions still remains challenging today. Nanoparticles functionalized with carbohydrates are one of the most powerful systems for studying carbohydrate-lectin interactions, because they mimic the multivalent presentation of carbohydrates encountered in nature, for example when viruses and bacteria bind to cells. On the basis of the model system glucose-Concanavalin A (ConA), we explore the application of Transient Magnetic Birefringence (TMB) to study these weak interactions, using glucose-functionalized colloidal magnetite nanoparticles (NPs) as probes. We demonstrate that the binding dynamics can be monitored and derive a model to obtain the apparent cooperativity. For our studies, we use nanoparticles of 6 and 8 nm in diameter. The ConA-generated response shows apparent cooperativity, due to the cross-linking of nanoparticles by the ConA tetramer which has four binding sites. Cooperativity is higher for 6 nm NPs, possibly due to a better accessibility of all four ConA binding sites on smaller NPs, enhancing cross-linking. For this system, we find a detection limit of 3-23 nM.


A workforce analysis informing medical school expansion, admissions, support for primary care, curriculum, and research.
This case study describes the findings of a physician workforce analysis and how an institution is using these findings to address the decreasing proportion of medical students choosing primary care careers. A University of Washington School of Medicine committee commissioned an analysis of the American Medical Association Physician Masterfile. The analysis examined physician-to-population ratios, rural-urban geographic distribution, physician demographics, and physician graduation from the university or one of its affiliated residency programs for graduates of allopathic medical schools and residencies at the county level in the 5 states in the WWAMI partnership (Washington, Wyoming, Alaska, Montana, and Idaho). The analysis found that in 2005, the 5 WWAMI states ranked at the bottom of US states in the number of publicly supported medical school and residency slots per capita. Although physician-to-population ratios were comparable to those in the rest of the country, the 5 WWAMI states imported most of their physicians, including family physicians, approximately 70% of whom came from other medical schools or residency programs. Family physicians were the only specialty distributed across the population gradient from urban to isolated rural areas. The workforce analysis is informing planning for medical school expansion, admissions, support for primary care, curriculum, and research at an institution with a clear mission that includes training the health workforce for its region. The analysis has wide potential applicability, but it has special relevance for primary care and has been particularly useful in making the case for supporting primary care education in the WWAMI region.


Overexpression of G protein-coupled receptors in cancer cells: involvement in tumor progression.
G protein-coupled receptors (GPCRs) play important roles in a variety of biological and pathological processes. They are considered among the most desirable targets for drug development. Recent studies have demonstrated that many GPCRs, such as endothelin receptors, chemokine receptors and lysophosphatidic acid receptors have been implicated in the tumorigenesis and metastasis of multiple human cancers. In this study, we conducted an in silico analysis of GPCR gene expression in primary human tumors by analyzing some publicly available gene expression profiling data. Statistical analysis was performed on eight microarray data sets of non-small cell lung cancer, breast cancer, prostate cancer, melanoma, gastric cancer and diffused large B cell lymphoma to identify GPCRs that are up-regulated in primary or metastatic cancer cells. Our analysis has demonstrated overexpression of several GPCRs in primary tumor cells, including chemokine receptors and protease-activated receptors that were shown to be important for tumorigenesis by previous studies. In addition, we have uncovered several GPCRs, such as neuropeptide receptors, adenosine A2B receptor, P2Y purinoceptor, calcium-sensing receptor and metabotropic glutamate receptors, that are expressed at a significantly higher level in some cancer tissue and may play a role in cancer progression. Analysis of cancer samples in different disease stages also suggests that some GPCRs, such as endothelin receptor A, may be involved in early tumor progression and others, such as CXCR4, may play a critical role in tumor invasion and metastasis. The present study demonstrates the value of publicly available microarray data as a resource to gain more understanding of cancer biology, to validate previous findings from in vitro experiments, and to identify potential novel anticancer targets and biomarkers.


Passage from stepwise to concerted dissociative electron transfer through modulation of electronic states coupling.
Reductive cleavage of the three cyanobenzyl chloride isomers in N,N-dimethylformamide gives new insights into the factors that control the mechanism during dissociative electron transfer. Within the family of investigated compounds, electrochemical reduction leads to expulsion of the chloride ion. While electron transfer is concerted with breaking of the C-Cl bond and acts as the rate-determining step in the case of both the ortho and para isomers, an intermediate anion radical is formed before rapid fragmentation in the case of the meta isomer. Such an unexpected mechanistic shift (all key thermodynamic parameters are very similar for the three chlorides) is interpreted in the framework of a modified version of the dissociative electron-transfer model that includes electronic coupling effects between the diabatic states of the products. These effects appear to control the very existence of a transient species along the reaction pathway.


A review of the effects of formaldehyde release from endodontic materials.
Formaldehyde is present in most living cells and the environment. In dentistry, patients may be exposed to formaldehyde through the use of several endodontic materials (e.g. AH 26) and during formocresol pulpotomies. This review outlines how the human body reacts to formaldehyde exposure, how recent data has relooked at the issue of carcinogenicity and leukaemia associated with formaldehyde, and whether it is possible to quantify the amount of formaldehyde produced by endodontic cements. The review analyses the way formaldehyde is produced from epoxy resins and addresses the question of whether the amount of formaldehyde from endodontic cements is large enough to override the body's ability to deal with its own endogenous levels of formaldehyde and should the amount of formaldehyde produced be a concern.


Metacognitive training in schizophrenia: from basic research to knowledge translation and intervention.
There has been a marked increase in the study of cognitive biases in schizophrenia, which has in part been stimulated by encouraging results with cognitive-behavioral interventions in the disorder. We summarize new evidence on cognitive biases thought to trigger or maintain positive symptoms in schizophrenia and present a new therapeutic intervention. Recent studies indicate that patients with paranoid schizophrenia jump to conclusions, show attributional biases, share a bias against disconfirmatory evidence, are overconfident in errors, and display problems with theory of mind. Many of these biases precede the psychotic episode and may represent cognitive traits. Building upon this literature, we developed a metacognitive training program that aims to convey scientific knowledge on cognitive biases to patients and provides corrective experiences in an engaging and supportive manner. Two new studies provide preliminary evidence for the feasibility and efficacy of this approach. The gap between our advanced understanding of cognitive processes in schizophrenia and its application in clinical treatment is increasingly being narrowed. Despite emerging evidence for the feasibility and efficacy of metacognitive training as a stand-alone program, its most powerful application may be in combination with individual cognitive-behavioral therapy.


Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review.
Despite substantial advancement in the understanding and treatment of chronic lymphocytic leukemia (CLL), a standard curative approach does not exist. The choice of treatment is generally based on the existence of biological and genetic factors associated with the prediction of prognosis, individual response to therapy, and duration of remission. About 20% of patients that require treatment have an aggressive disease course and die within a few years, despite early initiation of intensive therapy (poor-risk CLL). Poor-risk CLL can be predicted by the presence of genomic markers, and the quality and duration of response to purine-analogue-based treatment. Within this patient subgroup alternative treatment approaches such as alemtuzumab or new substances such as flavopiridol or IMiDs® should be considered. To date, the only treatment bearing curative potential is allogeneic stem cell transplantation; in contrast to conventional immunochemotherapy, it can provide long-term disease control, even in patients with del 17p or other unfavorable biological and clinical risk factors. The aim of this review was to outline the current strategies for the diagnosis and management of CLL, with a focus on high-risk CLL.