Serum amyloid A protein generates pre beta 1 high-density lipoprotein from alpha-migrating high-density lipoprotein.
Serum amyloid A protein (SAA), an acute-phase reactant in reactive amyloidosis, has high affinity for high-density lipoprotein (HDL). When SAA is added to HDL, SAA displaces apolipoprotein A-I (apoA-I) and phospholipid from the HDL particles. These dissociated components may form prebeta1-HDL because free apoA-I can associate with phospholipid to become a lipoprotein having prebeta mobility. To determine whether SAA generates prebeta1-HDL from alpha-migrating HDL, we investigated the effects of recombinant SAA on HDL subfraction concentration using nondenaturing two-dimensional gradient gel electrophoresis. When we added SAA (0.5 mg/mL) to plasma, the prebeta1-HDL concentration increased by 164% (from 4.7% +/- 1.3% to 12.4% +/- 3.2% of apoA-I, p < 0.005). The increase in prebeta1-HDL was proportional to the dose of SAA. When we added SAA to a column of Sepharose beads coupled to the isolated HDL (alpha-migrating HDL), prebeta1-HDL was dissociated from the column together with the SAA-associated HDL. In summary, we demonstrate that SAA generates prebeta1-HDL from alpha-migrating HDL. We speculate that SAA-mediated HDL remodeling may take place in inflammation.


Weekly carboplatin and docetaxel for locally advanced primary and recurrent cervical cancer: a phase I study.
The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated doses (MTDs) of a docetaxel-carboplatin regimen in patients with locally advanced cervical cancer (LACC) or recurrent cervical cancer. The regimen was administered weekly, with a maximum of 12 courses. Twenty patients were treated with with a total of 145 cycles of weekly carboplatin and docetaxel. The starting dose of docetaxel was 25 mg/m(2) with increments of 5 mg/m(2) until a final dose of 35 mg/m(2) was reached. Dose-escalation of docetaxel was followed by carboplatin at AUC 2, AUC 2.5, and AUC 3, respectively. Defined dose-limiting toxicities were WHO grade (G) 3 hematotoxicity, G4 mucositis, and G2 neurotoxicity. The response status of the patients was assessed using the common ECOG response criteria. Two of four patients developed a DLT at dose level 4. Nonhematological toxicity was generally mild, except for ubiquitous complete alopecia. The MTD was reached at docetaxel 35 mg/m(2) and carboplatin AUC 2 mg/mL.min. The overall response rate was 65% in the entire group of evaluable patients and 77% in patients with primary LACC, with two cases of pathological complete response. This dose-dense regimen was well-tolerated and could be administered on an outpatient basis.


Stage of disease progression moderates the association between social support and depression in prostate cancer survivors.
This study was designed to test the association between social support and depression at different stages of disease progression in men with prostate cancer.Seventy-one men with prostate cancer completed measures of social support and depression three times: T1 (at baseline), T2 (T1 + 2 months), and at T3 (T1 + 4 months). Stage of disease progression was significantly associated with increasing symptoms of depression. Stage of disease progression also moderated the association between social support and depression. Social support was associated with a subsequent worsening of depression for men with early-stage disease. For men with more advanced prostate cancer, social support was associated with improvements in subsequent depression. Social support has different prognostic value for psychological distress among men with prostate cancer depending upon the stage of their disease.


Waveguide-Integrated, Plasmonic Enhanced Graphene Photodetectors.
We present a micrometer-scale, on-chip integrated, plasmonic enhanced graphene photodetector (GPD) for telecom wavelengths operating at zero dark current. The GPD is designed to directly generate a photovoltage by the photothermoelectric effect. It is made of chemical vapor deposited single layer graphene, and has an external responsivity ∼12.2 V/W with a 3 dB bandwidth ∼42 GHz. We utilize Au split-gates to electrostatically create a p-n-junction and simultaneously guide a surface plasmon polariton gap-mode. This increases the light-graphene interaction and optical absorption and results in an increased electronic temperature and steeper temperature gradient across the GPD channel. This paves the way to compact, on-chip integrated, power-efficient graphene based photodetectors for receivers in tele- and datacom modules.


[Cloning, expression and characterization of a novel esterase from marine sediment microbial metagenomic library].
To clone, express and characterize a novel esterase from marine sediment microbial metagenomic library. Using esterase segregation agar containing tributyrin, we obtained esterase positive fosmid clone FL10 from marine sediment microbial metagenomic library. This fosmid was partially digested with Sau3A I to construct the sublibrary, from which the esterase positive subclone pFLS10 was obtained. The full length of the esterase gene was amplified and cloned into the expressing vector pET28a, and the recombinant plasmid was transformed into E. coli BL21 cells. We analyse the enzyme activity and study the characterization of the esterase after its expression and purification. An ORF (Open Reading Frame) of 924 bp was identified from the subclone pFLS10. Sequence analysis indicated that it showed 71% amino acid identity to esterase (ADA70030) from a marine sediment metagenomic library. The esterase is a novel low-temperature-active esterase and had highest lipolytic activity to the substrate of 4-nitrophenyl butyrate (C4). The optimum temperature of the esterase was 20 degrees C, the optimum pH was 7.5. The esterase in this study had good thermostability at 20 degrees C and good pH stability at pH8 -10. Significant increase in lipolytic activity was observed with addition of K+ and Mg2+, while decrease with Mn2+ etc. We obtained the novel esterase gene fls10 from the marine sediment microbial metagenomic library. The esterase had good thermostability and high lipolytic activity at low temperature and under basic conditions, which laid a basis for industrial application.


Changing nursing practice through reflection on the Roper, Logan and Tierney model: the enhancement approach to action research.
To the clinical practitioner both nursing models and nursing research may currently be highly valued by practitioners or managers. Yet, by facilitating group reflection on the nursing model identified in the ward philosophy and adopting the enhancement approach to action research, surgical nurses were empowered to effect change and, consequently, to enhance the quality of patient care in their ward. The study was undertaken in two phases over a 15-month period and utilized a multi-method approach. In phase 1 triangulation of the data enabled the practitioners/co-researchers to identify and reflect on patients' psychological needs within the independence/dependence continuum of the Roper et al. (1990) model. Phase 2 involved a collaborative approach to the planning, implementation and evaluation of innovations which resulted from reflection on practice. Nurse-doctor relationships including anaesthetist noncompliance were, though, a controversial issue. Collaborative practice was undermined by the co-researchers' ambivalence concerning feedback from the medical staff. Overall, however, the individual contribution of each co-researcher was recognized and valued. They had both choice and control which enabled them to develop personally and professionally. Group reflection was seen as essential feedback strategy during the change process.


[Toxic anterior segment syndrome].
Toxic anterior segment syndrome is a sterile postoperative inflammatory reaction, with typical clinical features and serious secondary complications. The causes of TASS are numerous and varied. It is informed that irrigating solutions and ophthalmic viscosurgical devices, ophthalmic instrument contaminants, ocular medications and intraocular lenses are correlation factors. TASS is easy to be confused with the infectious endophthalmitis and difficult to diagnose. It is reported that the steroid therapy for TASS is effective but the mainstay of treatment for TASS centers on prevention.


HnRNP A1/A2 and SF2/ASF regulate alternative splicing of interferon regulatory factor-3 and affect immunomodulatory functions in human non-small cell lung cancer cells.
Heterogeneous nuclear ribonucleoparticule A1/A2 (hnRNP A1/A2) and splicing factor 2/alternative splicing factor (SF2/ASF) are pivotal for precursor messenger RNA (pre-mRNA) splicing. Interferon regulatory factor-3 (IRF-3) plays critical roles in host defense against viral and microbial infection. Truncated IRF-3 proteins resulting from alternative splicing have been identified and characterized as functional antagonists to full-length IRF-3. In this study, we examined the molecular mechanism for splicing regulation of IRF-3 pre-mRNA and first reported the regulatory effect of hnRNP A1/A2 and SF2/ASF on IRF-3 splicing and activation. RNA interference-mediated depletion of hnRNP A1/A2 or SF2/ASF in human non-small cell lung cancer (NSCLC) cells increased exclusion of exons 2 and 3 of IRF-3 gene and reduced expression levels of IRF-3 protein and IRF-3 downstream effector molecules interferon-beta and CXCL10/IP-10. In addition, direct binding of hnRNP A1 and SF2/ASF to specific binding motifs in IRF-3 intron 1 was confirmed by RNA electrophoretic mobility shift assay. Subsequent minigene splicing assay showed that IRF-3 minigenes with mutated hnRNPA 1/A2 or SF2/ASF binding motifs increased exclusion of exons 2 and 3. Moreover, knockdown of hnRNP A1/A2 or SF2/ASF in NSCLC cells reinforced phytohemagglutinin-induced tumor necrosis factor-alpha release by peripheral blood mononuclear cells (PBMC) but suppressed that of interleukin-10 in NSCLC/PBMC co-cultures. Taken together, our results suggest that specific knockdown for hnRNP A1/A2 or SF2/ASF increase exclusion of exons 2 and 3 of IRF-3 pre-mRNA and influence immunomodulatory functions of human NSCLC cells.


Salvage camrelizumab plus apatinib for relapsed esophageal neuroendocrine carcinoma after esophagectomy: a case report and review of the literature.
The current evidence regarding immunotherapy plus targeted therapy in esophageal neuroendocrine carcinoma (NEC) is lacking. Camrelizumab is a programmed cell death protein 1 inhibitor. Apatinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. A 50-year-old female was initially diagnosed as primary esophageal NEC. Neoadjuvant chemotherapy and Ivor Lewis esophagectomy were performed (ypT3N0M0, stage Ⅱ). Twenty months after the surgery, an isolated mediastinal lymph node recurrence of NEC was recorded. The specimen revealed a positive expression of vascular endothelial growth factor and programmed cell death ligand 1. The diseased lymph node was slightly enlarged after two cycles of first-line paclitaxel liposome and S-1. Second-line apatinib and S-1 for 2 months also resulted in progressive disease. Subsequently, third-line camrelizumab plus apatinib was continued for 5 months. The patient demonstrated a progression-free status for more than 10 months following the combination therapy. Meanwhile, relevant studies of camrelizumab in gastric or esophageal cancer were briefly reviewed. Based on the current evidence, camrelizumab is a promising agent for esophageal cancer. More prospective trials are warranted before a definite recommendation could be drawn.


MedEval - A Swedish medical test collection with doctors and patients user groups.
Test collections for information retrieval are scarce. Domain specific test collections even more so, and medical test collections in the Swedish language non-existent prior to the making of the MedEval test collection. Most research in information retrieval has been performed in the English language, thus most test collections contain English documents. However, English is morphologically poor compared to many other European languages and a number of interesting and important aspects have not been investigated. Building a medical test collection in Swedish opens new research opportunities. This article describes the making of and potential uses of MedEval, a Swedish medical test collection with assessments, not only for topical relevance, but also for target reader group: Doctors or Patients. A user of the test collection may choose if she wishes to search in the Doctors or the Patients scenario where the topical relevance assessments have been adjusted with consideration to user group, or to search in a scenario which regards only topical relevance.In addition to having three user groups, MedEval, in its present form, has two indexes, one where the terms are lemmatized and one where the terms are lemmatized and the compounds split and the constituents indexed together with the whole compound. Differences discovered between the documents written for medical professionals and documents written for laypersons are presented. These differences may be utilized in further studies of retrieval of documents aimed at certain groups of readers. Differences between the groups of documents are, for example, that professional documents have a higher ratio of compounds, have a greater average word length and contain more multi-word expressions.An experiment is described where the user scenarios have been utilized, searching with expert terms and lay terms, separately and in combination in the different scenarios. The tendency discovered is that the medical expert gets best results using expert terms and the lay person best results using lay terms, but also quite good results using expert terms or lay and expert terms in combination. The many features of MedEval gives a variety of research possibilities, such as comparing the effectiveness of search terms when it comes to retrieving documents aimed at the different user groups or to study the effect of compound decomposition in retrieval of documents. As Swedish, the language of MedEval, is a morphologically more complex language than English, it is possible to study additional aspects of the effect of natural language processing in information retrieval, for example utilizing different inflectional word forms in the retrieval of expert vs lay documents. MedEval is the first Swedish test collection of the medical domain. The Department of Swedish at the University of Gothenburg is in the process of making the MedEval test collection available to academic researchers.


Affinity capture using peptide-functionalized magnetic nanoparticles to target Staphylococcus aureus.
Staphylococcus aureus, a commonly found pathogen, can cause food poisoning and infections. Thus, it is necessary to develop analytical methods for the rapid screening of S. aureus in suspicious samples. Magnetic nanoparticles (MNPs) are widely used as affinity probes to selectively enrich target species from complex samples because of their high specific surface area and magnetic properties. The MNP surface should be functionalized to have the capability to target specific species. We herein propose a straightforward method to functionalize aluminum oxide-coated iron oxide (Fe3O4@Al2O3) MNPs with the peptide HHHHHHDEEGLFVD (D). The peptide D was comprised of three domains: polyhistidine (H6) used as the linker, DEE added as the spacer, and GLFVD used for targeting S. aureus. D was immobilized on the surface of Fe3O4@Al2O3 MNPs through H6-Al chelation. Our results showed that the D-functionalized Fe3O4@Al2O3 MNPs (D-Fe3O4 MNPs) possess the capability to target S. aureus. The selective trapping experiments were conducted under microwave-heating for only 60 s, and sufficient bacterial cells were trapped by the MNPs to be identified by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). We demonstrated that the D-Fe3O4@Al2O3 MNPs combined with MALDI-MS can be used to rapidly characterize trace amounts of S. aureus in complex juice and egg samples.


Effect of viruses and interferon on chick embryo otocyst cultures.
Chick embryo otocyst organ cultures were subjected to live vesicular stomatitis virus and rubella virus preparations, to interferon (IFN), and to a combination of both virus and IFN, and compared to control untreated otocysts. We observed morphologic and microscopic changes suggestive of individual cell death and delayed organ differentiation in the virus-treated groups, along with an appreciable decrease in size of the otocyst. Low-dose IFN treatment prior to virus inoculation appeared to partially prevent these effects. The addition of IFN alone did not seem to affect the differentiation process. Time-lapse videophotography further confirmed the above findings. This study suggests that the peripheral component of congenital deafness associated with viral infections is likely to be an effect of the virus itself, and not of the IFN. Interferon provides a partial protective effect against the insult from the virus in vitro and does not seem to be toxic to the developing otocyst.


Clinical spectrum and natural history of isolated mitral valve prolapse in 30 children.
Thirty pediatric patients with isolated mitral valve prolapse were studied in order to elucidate the clinical manifestations and the natural history of this condition in children. The mean age at the time of diagnosis was 9.5 years, with a mean follow-up of 5 years. The evaluation of all 30 patients included: clinical examination by a pediatric cardiologist, ECG, chest X-ray, echocardiography and Holter monitoring. Two patients underwent cardiac catheterization and angiography, and two patients required antiarrhythmic medication for symptomatic ventricular tachycardia. No progression of mitral insufficiency was observed during the follow-up period. There were no instances of subacute bacterial endocarditis, cerebral vascular accident or sudden death. The prognosis of mitral valve prolapse appears to be favorable in childhood.


A Performance Analysis of Long-term Acute-Care Hospitals Owned by Large, Multistate Investor-Owned Companies.
This study provides a descriptive assessment of the operating performance of for-profit long-term acute-care hospitals owned by multistate, investor-owned companies (large FP LTCHs) compared with FP LTCHs owned by smaller FP companies (small FP LTCHs) and nonprofit LTCHs (NP LTCHs). The study used the Centers for Medicare & Medicaid Services cost report data for 290 LTCHs from 2010 through 2012 to compare the financial performance of large and small FP LTCHs and NP LTCHs. The study found that the median operating profit margin for large FP LTCHs was 8.06%, which was twice as high as that of the small FP LTCHs and NP LTCHs (4.78% and 2.80%, respectively). Larger size, serving a greater proportion of private pay and more complex patients and incurring lower operating expenses, including salary expenses, may account for the higher operating margin of the large FP LTCHs.


Studies on the efficacy of mast cell growth factor (c-kit ligand) in vitro as well as in vivo.
We tested the ability of recombinant human (rhu) mast cell growth factor (MGF), also known as c-kit ligand, to stimulate the colony formation of human bone marrow cells in semisolid medium alone and in combination with rhu erythropoietin (EPO), rhu Interleukin 3 (IL-3), rhu granulocyte colony stimulating factor (G-CSF) and rhu granulocyte-macrophage colony stimulating factor (GM-CSF). The addition of MGF to cultures containing EPO or EPO + IL-3, GM-CSF and G-CSF, resp., resulted in macroscopic erythroid burst-forming units (BFU-E). Multipotential (colony-forming unit granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]) progenitors were stimulated by MGF in the presence of EPO. Colony-forming unit granulocyte-macrophage (CFU-GM) were activated by MGF only in combination with GM-CSF. The combination of MGF with EPO was used for synergism studies in healthy cynomolgus monkeys. In the chosen concentration MGF alone had no effect on white blood cell (WBC) counts and on platelets, but a slight effect on reticulocytes. EPO by itself increased reticulocyte counts with no effects on WBC or platelets. The combination of both factors resulted in a significant increase of reticulocytes. No other effects were seen. These studies demonstrate the potent synergistic interaction of MGF and other hematopoietic growth factors.


[Comparison of physical growth in school-children living in children's residential facilities and in families with emphasis on the gypsy ethnic group].
The authors investigated the growth of 1208 gipsy and non-gipsy children living with their families and in childrens homes. They revealed that gipsy children from childrens homes were shorter, lighter and had a smaller chest circumference as compared with gipsy children living with their families. This applied only to younger school children. Somatic development caught up in boys at the age of 11-12 years and in girls approximately 1-2 years sooner. The values of the body mass index in boys declined with age. In girls this decline was found only up to the age of 11 to 12 years. Non-gipsy children from childrens homes were smaller than non-gipsy children according to Slovak standards (Lipková et al.; 5); this was particularly marked in boys. The authors found also that the somatic development of gipsy children from childrens homes oscillates between the somatic development of non-gipsy children according to the Slovak standards and the somatic development of gipsy children from families but only during later school age.


Growth inhibition of Mycobacterium avium complex in human alveolar macrophages by the combination of recombinant macrophage colony-stimulating factor and interferon-gamma.
The reservoir of Mycobacterium avium complex (MAC) during human infection is the mononuclear phagocyte. In these studies, the ability of certain macrophage-active cytokines to affect MAC growth in human alveolar macrophages was evaluated. Neither recombinant interferon-gamma (2 x 10(2) to 10(3) U/well of 5 x 10(5) cells) nor recombinant macrophage colony-stimulating factor (20 to 50 ng/well), when tested alone, exhibited a consistent ability to induce macrophage targets to inhibit the growth of a clinical strain of MAC serovar 4. However, the combination of these cytokines (1 to 50 ng macrophage colony-stimulating factor + 10(3) U interferon per well) was remarkably effective in diminishing replication of MAC in all experiments. These cytokines were also able to induce alveolar macrophages to restrict MAC growth even though cells were obtained from several individuals with acquired immunodeficiency syndrome (AIDS) or from normal donors and infected in vitro with the human immunodeficiency virus type 1. The effect of this cytokine combination was not abrogated by 10(4) neutralizing U/ml of anti-tumor necrosis factor-alpha antibody. Rather, the combination of interferon-gamma and macrophage colony-stimulating factor appeared to activate intrinsic macrophage mechanisms for restricting MAC growth and deserves further study to determine the potential value of this cytokine combination in the treatment of human infection.


Evaluation of haemoparasite and Sarcocystis infections in Australian wild deer.
Wild animals are natural reservoir hosts for a variety of pathogens that can be transmitted to other wildlife, livestock, other domestic animals, and humans. Wild deer (family Cervidae) in Europe, Asia, and North and South America have been reported to be infected with gastrointestinal and vector-borne parasites. In Australia, wild deer populations have expanded considerably in recent years, yet there is little information regarding which pathogens are present and whether these pathogens pose biosecurity threats to humans, wildlife, livestock, or other domestic animals. To address this knowledge gap, PCR-based screening for five parasitic genera was conducted in blood samples (n = 243) sourced from chital deer (Axis axis), fallow deer (Dama dama), rusa deer (Rusa timorensis) and sambar deer (Rusa unicolor) sampled in eastern Australia. These blood samples were tested for the presence of DNA from Plasmodium spp., Trypanosoma spp., Babesia spp., Theileria spp. and Sarcocystis spp. Further, the presence of antibodies against Babesia bovis was investigated in serum samples (n = 105) by immunofluorescence. In this study, neither parasite DNA nor antibodies were detected for any of the five genera investigated. These results indicate that wild deer are not currently host reservoirs for Plasmodium, Trypanosoma, Babesia, Theileria or Sarcocystis parasites in eastern Australia. We conclude that in eastern Australia, wild deer do not currently play a significant role in the transmission of these parasites. This survey represents the first large-scale molecular study of its type in Australian wild deer and provides important baseline information about the parasitic infection status of these animals. The expanding populations of wild deer throughout Australia warrant similar surveys in other parts of the country and surveillance efforts to continually assess the level of threat wild deer could pose to humans, wildlife, livestock and other domestic animals.


Vaccinal effect of HIV-1 antibody therapy.
The review recalls recent findings regarding the induction of vaccinal effects by HIV-1 broadly neutralizing antibodies (bNAbs) and highlights potential therapeutic strategies to exploit such immunomodulatory properties. Studies in different animal models have shown that mAbs can generate long-lasting protective immunity. Induction of this vaccinal effect by HIV-1 bNAbs has also been more recently reported in animal models of HIV-1 infection. Notably, bNAbs treatment of macaques infected with the chimeric simian-human immunodeficiency virus (SHIV) improved both humoral and cellular adaptive immune responses that contributed to disease control. Importantly, this concept has been extended to HIV-1-infected patients as enhancement of humoral responses was recently reported in HIV-1 patients treated with bNAbs. Studies aiming at elucidating the mechanisms underlying these immunomodulatory properties of bNAbs have identified a role for immune complexes in shaping immune responses against HIV-1. They also highlight different Fc (fragment crystallizable) region effector functions that might be required for the enhancement of HIV-1 immune responses upon bNAbs treatment. HIV-1 bNAbs can elicit protective adaptive immune responses through mechanisms involving multiple cellular and molecular actors of the immune system. Harnessing these mechanisms will be crucial to achieve protective immunity against HIV-1 infection by bNAbs.


The use of dopaminergic and stimulant drugs for the treatment of depression.
The brain reward system consists of extensive neural pathways that mediate reward behavior such as pleasure and motivation. These pathways may be involved in the development of symptoms such as apathy, anhedonia, and cognitive dysfunction seen in patients with major depression. These pathways are served primarily, although not exclusively, by the chemical neurotransmitter dopamine, which has suggested a therapeutic role for drugs that influence dopamine activity. A small number of clinical trials using various dopaminergic and stimulant drugs for the treatment of major depression and bipolar depression have demonstrated some benefit when combined with standard antidepressant drugs. Based on this work, several ongoing trials are investigating the use of the stimulant drug lisdexamfetamine (Vyvanse®) as an adjunctive treatment for depression.


Recent advances in surgery of the temporal bone and skull base.
Remarkable advances have been made in the field of neuro-otologic and skull base surgery within the past decade. Each component of the "disease model"--prevention, diagnosis, therapy, and rehabilitation--is undergoing rapid progress. The purpose of this paper is to highlight only a few of these achievements. Each topic chosen has witnessed recent advancement in one aspect of the disease model. Neurofibromatosis (prevention) has been subjected to chromosomal mapping, allowing for genetic counseling. Intraoperative facial nerve monitoring (diagnosis) has allowed improved anatomic and functional preservation of this nerve during surgery. Embolization of glomus tumors (therapy) has rendered these difficult lesions more surgically manageable, and cochlear implantation (rehabilitation) has allowed the profoundly deaf to play a more active role in society. Each of these topics is briefly discussed as it relates to the temporal bone surgeon.


[Severe trauma in children].
Trauma are responsible for approximately 50% of the deaths of the pediatric population between 1-15 years of age. This high mortality rate, associated with frequent sequelae, leading sometimes to severe handicaps, is a major problem of public health in the developed countries. Pediatric trauma have some particularities, due to anatomical and physiological differences, and to specific injury mechanisms. Management of a patient with severe trauma is best performed by trained physicians, working in a multidisciplinary team with a two steps approach: 1) emergency rapid clinical assessment and resuscitation. 2) a secondary complete clinical evaluation associated with medical imaging, mainly based on CT scan. Head injuries are frequent and represent the main prognosis factor, mass lesions being less frequent and cerebral oedema more frequent in children, than in adult; brain swelling appears to be less frequent than initially reported. Management of head trauma has evolved in recent years, and is now largely directed towards the prevention of secondary ischemic brain injury: new monitoring devices are proposed to pursue that goal: transcranial doppler and continuous jugular vein oxygen saturation monitoring. Spinal cord injuries are rare but may be severe: cervical and spinal cord injuries without radiological abnormality (SC/WORA) appear to be more frequent than in adult. Most often, abdominal plain viscera injuries are treated with a conservative non operative approach. Among chest injuries, pulmonary contusion is the most frequent, with a favorable outcome in most cases within 3-4 days. Child abuse must be suspected in any case where there is no clear injury mechanism or when there is a discrepancy between the severity of the injury and the alleged mechanism.


Direct measurement of the free cyclotron frequency of a single particle in a Penning trap.
A measurement scheme for the direct determination of the free cyclotron frequency ν(c) of a single particle stored in a Penning trap is described. The method is based on the dressed states of mode coupling. In this novel measurement scheme both radial modes of the single trapped particle are simultaneously coupled to the axial oscillation mode.


The Sexual Dimorphism of Lipid Kinetics in Humans.
In addition to the obvious differences in body shape, there are substantial differences in lipid metabolism between men and women. These differences include how dietary fatty acids are handled, the secretion and clearance of very low-density lipoprotein-triglycerides, the release rates of free fatty acids (FFA) from adipose tissue relative to energy needs, and the removal of FFA from the circulation, including the storage of FFA into adipose tissue via the direct uptake process. We will review what is known about these processes and how they may contribute to the sexual dimorphism of body fat distribution.


[Defect at uterine incision from prior Caesarean section].
A case of asymptomatic uterine fenestration in 26+3 gestational weeks in a patient who had previously undergone Caesarean section is presented. Controls were planned. In gestational week 34+1 the woman was hospitalized due to lower abdominal pain, but with otherwise normal objective parameters. Ten days later the patient had increasing pain, and a caesarean section was performed. Fenestration was confirmed. This leads to reflections on how to treat and observe such cases, and further discussion about whether early identification of risk patients by ultrasound is possible.


Caregivers' Willingness to Vaccinate Their Children against Childhood Diseases and Human Papillomavirus: A Cross-Sectional Study on Vaccine Hesitancy in Malawi.
Vaccines are among the most effective and cost-efficient public health interventions for promoting child health. However, uptake is considerably affected by vaccine hesitancy. An example is Malawi, with a decline in second vaccine doses and the highest cervical cancer incidence and mortality rate in Sub-Saharan Africa. Understanding vaccine hesitancy is especially important when new vaccines are introduced. This study explores factors contributing to vaccine hesitancy for routine childhood immunization and the human papillomavirus vaccine in Malawi. The study used a cross-sectional survey design targeting caregivers of children under five years old and adolescent girls. The sample population was derived using three inclusion criteria: one district with low vaccine uptake (Dowa), one district with high vaccine uptake (Salima), and one district where human papillomavirus vaccine was piloted earlier (Zomba). A convenience sample of one primary and one secondary health facility was selected within each district, and participants were systematically included (n = 600). The measures were based on 5C scale for measuring vaccine hesitancy. Multiple regression analyses were performed to explore vaccination intention predictors. Confidence in vaccine safety was the strongest predictor of routine childhood immunization, followed by constraints due to everyday stress. Caregivers had lower confidence in vaccine safety and efficacy when they believed rumors and misinformation and were unemployed. Confidence was higher for those who had more trust in healthcare workers. Age, gender, religion, education, employment, belief in rumors, and trust in healthcare workers were considered predictors of vaccination intention. A husband's positive attitude (approval) increased childhood vaccination intention. For human papillomavirus, vaccination intentions were higher for those with lower education, more trust in healthcare workers, lower complacency, and a lower tendency toward calculating the benefits and risks of vaccination. Knowledge of human papillomavirus did not increase vaccination intention, but the need to attain a husband's approval did. Being a young adult and unemployed increased belief in rumors, while trust in healthcare workers reduced the belief. This study provides good insights into the drivers of vaccine hesitancy across different contexts in Malawi. However, further studies are necessary to understand low risk perception among elderly people and the declining trend in second vaccine doses.


Metric learning for comparing genomic data with triplet network.
Many biological applications are essentially pairwise comparison problems, such as evolutionary relationships on genomic sequences, contigs binning on metagenomic data, cell type identification on gene expression profiles of single-cells, etc. To make pair-wise comparison, it is necessary to adopt suitable dissimilarity metric. However, not all the metrics can be fully adapted to all possible biological applications. It is necessary to employ metric learning based on data adaptive to the application of interest. Therefore, in this study, we proposed MEtric Learning with Triplet network (MELT), which learns a nonlinear mapping from original space to the embedding space in order to keep similar data closer and dissimilar data far apart. MELT is a weakly supervised and data-driven comparison framework that offers more adaptive and accurate dissimilarity learned in the absence of the label information when the supervised methods are not applicable. We applied MELT in three typical applications of genomic data comparison, including hierarchical genomic sequences, longitudinal microbiome samples and longitudinal single-cell gene expression profiles, which have no distinctive grouping information. In the experiments, MELT demonstrated its empirical utility in comparison to many widely used dissimilarity metrics. And MELT is expected to accommodate a more extensive set of applications in large-scale genomic comparisons. MELT is available at https://github.com/Ying-Lab/MELT.


Glucuronidation of 7-hydroxy-4-methylcoumarin by microsomes from normal and diseased human livers.
Glucuronidation of 7-hydroxy-4-methylcoumarin (7-H-4-MC) by microsomal UDP-glucuronosyltransferases from 12 human liver biopsy samples was studied. Glucuronidation rates were highest for livers with mild cholestasis while those for livers with mild fatty changes were similar to normal livers. The lowest rates were exhibited by livers showing primary or metastatic carcinoma on histological examination. Thus, glucuronidation of not only bile acids but also of other substrates such as 7-H-4-MC may be elevated in cholestasis. These results are also consistent with other studies stating that glucuronidation might be spared in certain mild hepatic diseases.


[Future scope for gene therapy for liver metastasis of colon cancer].
Liver metastasis is the most serious event for physicians and surgeons treating patients with colorectal cancer. Gene therapy is expected to become a novel strategy to prevent liver metastasis. Four types of clinical studies are currently underway: 1) suicide-gene therapy with the cytosine deaminase gene; 2) immune gene therapy with cytokine (inter leukin-2) or major histocompatibility complex class I gene HLA-B7; 3) tumor suppressor gene p53 therapy; and 4) lysis of p53 mutant cancer cells with E1B55k-deleted adenovirus (Onyx-015). Basic research provided several candidates for the liver metastasis-associated genes, including MMP7, DCC, CDC25B, E-cadherin, CD44, vascular endothelial growth factor, etc. There is an alternative approach to liver metastasis, which attempts to introduce a specific gene such as cytosine deaminase and TIMP-2 into the hepatocytes but not into the tumor itself. This concept is based on results showing that hepatocytes can incorporate genes more readily than cancer cells can. Recently, mutant virus therapy has been developed, which includes Onyx-015, adenovirus dl922-947, and mutant-type herpes simplex virus. These mutant types of virus specifically proliferate in the cancer cells and result in their lysis. In the future, development of gene delivery systems that are powerful and specific to cancer type is essential.


Trauma recidivism in a large urban canadian population.
Prevention of trauma might be achieved by risk factor modification. Identification of such risk factors can be pursued by various means. Trauma recidivists may possess and highlight risk factors. Accordingly, trauma recidivists were analyzed as a method to elucidate trauma risk factors. A retrospective analysis of 13,057 trauma patients in Toronto was conducted. Forty-two recidivists were identified, and their first admission was compared with a control group of 84 non-recidivists. The rate of trauma recidivism was 0.38% overall. Trauma recidivists were more likely to be from the inner city, male, homeless, suffering from chronic medical conditions. In addition, psychiatric conditions, an alcoholism history or any alcohol at the time of injury, intentionally injured, or engaged in criminal activity were also significantly more common in recidivists (p <0.05). Risk factors for major trauma can be identified by analyzing recidivists in a large urban Canadian population.


Comparison of Hospital-at-Home models: a systematic review of reviews.
To provide an overview of the safety and effectiveness of Hospital-at-Home (HaH) according to programme type (early-supported discharge (ESD) vs admission avoidance (AA)), and identify the model with higher evidence for addressing clinical, length of stay (LOS) and cost outcomes. A systematic review of reviews was conducted by performing a search on PubMed, EMBASE, Cochrane Database of Systematic Reviews, Web of Science and Scopus (January 2005 to June 2020) for English-language systematic reviews evaluating HaH. Data on primary outcomes (mortality, readmissions, costs, LOS), secondary outcomes (patient/caregiver outcomes) and process indicators were extracted. Quality of the reviews was assessed using Assessment of Multiple Systematic Reviews-2. There was no registered protocol. Ten systematic reviews were identified (four high quality, five moderate quality and one low quality). The reviews were classified according to three use cases. ESD reviews generally revealed comparable mortality (RR 0.92-1.03) and readmissions (RR 1.09-1.25) to inpatient care, shorter hospital LOS (MD -6.76 to -4.44 days) and unclear findings for costs. AA reviews observed a trend towards lower mortality (RR 0.77, 95% CI 0.54 to 1.09) and costs, and comparable or lower readmissions (RR 0.68-0.98). Among reviews including both programme types (ESD/AA), chronic obstructive pulmonary disease reviews revealed lower mortality (RR 0.65-0.68) and post-HaH readmissions (RR 0.74-0.76) but unclear findings for resource use. For suitable patients, HaH generally results in similar or improved clinical outcomes compared with inpatient treatment, and warrants greater attention in health systems facing capacity constraints and rising costs. Preliminary comparisons suggest prioritisation of AA models over ESD due to potential benefits in costs and clinical outcomes. Nonetheless, future research should clarify costs of HaH programmes given the current low-quality evidence, as well as address evidence gaps pertaining to caregiver outcomes and adverse events under HaH care.


Tumour-infiltrating lymphocyte density is associated with favourable outcome in patients with advanced non-small cell lung cancer treated with immunotherapy.
The established role of morphological evaluation of tumour-infiltrating lymphocytes (TILs) with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) is unknown. We aimed to determine TIL association with the outcome for ICIs and for chemotherapy in advanced NSCLC. This is a multicenter retrospective study of a nivolumab cohort of 221 patients treated between November 2012 and February 2017 and a chemotherapy cohort of 189 patients treated between June 2009 and October 2016. Patients with available tissue for stromal TIL evaluation were analysed. The presence of a high TIL count (high-TIL) was defined as ≥10% density. The primary end-point was overall survival (OS). Among the nivolumab cohort, 64% were male, with median age of 63 years, 82.3% were smokers, 77% had performance status ≤1 and 63% had adenocarcinoma histology. High-TIL was observed in 22% patients and associated with OS (hazard ratio [HR] 0.48; 95% confidence interval [95% CI]: 0.28-0.81) and progression-free survival [PFS] (HR = 0.40; 95% CI: 0.25-0.64). Median PFS was 13.0 months (95% CI: 5.0-not reached) with high-TIL versus 2.2 months (95% CI: 1.7-3.0) with the presence of a low TIL count (low-TIL). Median OS for high-TIL was not reached (95% CI: 12.2-not reached) versus 8.4 months (95% CI: 5.0-11.6) in the low-TIL group. High-TIL was associated with the overall response rate (ORR) and disease control rate (DCR) (both, P < .0001). Among the chemotherapy cohort, 69% were male, 89% were smokers, 86% had performance status ≤1 and 90% had adenocarcinoma histology. High-TIL was seen in 37%. Median PFS and OS were 5.7 months (95% CI: 4.9-6.7) and 11.7 months (95% CI: 9.3-13.0), respectively, with no association with TILs. High-TIL was associated with favourable outcomes in a real-world immunotherapy cohort of patients with NSCLC, but not with chemotherapy, suggesting that TILs may be useful in selecting patients for immunotherapy.


[From the pharmacology of drugs to their use: formation of knowledge about psychotropic drugs].
Drug effects are complex events in drug users' lives. What do we know about the effects of major psychotropic drugs, and how have we arrived at this knowledge? An exercise is presented herein that assists the reader in assessing the state of her or his knowledge about the effects of certain psychotropic drugs. The exercise format allows the reader to explore how their and others' knowledge about psychotropic drugs are constructed, by examining cellular, organal, behavioral, and social levels of experience for specific drugs. Examples of effects for five specific drugs, identified from a variety of sources, are presented and described in the context of these different levels of experience.


Psychological skill model of collegiate athletes in Taiwan.
The importance of psychological skills to an athlete is widely recognized. The Athletic Psychological Skills Inventory (APSI) was developed to evaluate psychological skills in the Taiwanese sports environment. This study employed the APSI model to refine the psychological skill factor structure. The model was supported as a reliable and valid form of measurement. A second-order confirmatory factor analysis (CFA) confirmed the factor structure of the APSI in Taiwanese collegiate athletes. Peaking under pressure and coping with adversity were combined into a simplified factor, coping with adversity.


Healthcare safety committee in Japan: mandatory accountability reporting system and punishment.
The publication of To Err is Human by the Institute of Medicine highlighted the increased international concern about patient safety. Each country has developed its own medical adverse event reporting system. In 2007, the Japanese government attempted to establish a new accountability system in medicine, after an obstetrician was arrested for manslaughter. This paper reviews how this accountability system affected Japanese physicians' behavior, and describes different types of medical adverse event reporting systems. In general, reporting of adverse event systems can be either mandatory or voluntary, with the purpose being either for learning or for accountability. The goal of a newly proposed mandatory accountability system from the Japanese government was to investigate the cause of death in medical cases in order to clarify liability. Reports generated by this system could potentially be cited in civil law suits, administrative sanctions, and criminal prosecutions. After announcement of this new system, Japanese physicians began to act defensively, fearing criminal prosecution. Refusing to see high-risk patients and 'bouncing' (sometimes referred to as 'turfing' or 'dumping') to other hospitals became national phenomena. In addition, medical school graduates began avoiding highly legally vulnerable specialties. Even though this new system is not yet legalized in Japan, at least 153 obstetrics hospitals and 3320 clinics have closed. The new system of investigating medical adverse events in Japan allows for incident reports to be utilized in court. This has led to widespread fear of prosecution and defensive medicine. The lessons from Japan should be considered when other countries implement nationwide accountability systems.


Transcatheter closure of atrial septal defect using self-expandable septal occluder.
Transcatheter closure of atrial septal defect is an accepted alternative to surgical closure. It was attempted in 63 patients (age range 1.5-55 years) using self-expandable Amplatzer septal occluder (AGA Med. Co., USA). The atrial septal anatomy was evaluated by transthoracic and multiplane transoesophageal echocardiography with special reference to septal margins and adjacent structures. The size of atrial septal defect on echocardiographic evaluation varied from 9-28 (17.5 +/- 4.7) mm. Fifty (79.4%) patients had adequate septal margins of 5 mm or larger, while remaining 13 (20.6%) had insufficient anterosuperior margin. Cardiac catheterisation revealed Qp/Qs ranging from 1.5 to 5.3 and balloon-stretched atrial septal defect diameter of 10-32 (20.3 +/- 5.3) mm. The procedure was overall successful in 62 (98.4%) patients and in all patients with insufficient anterosuperior margin. Embolisation of the device occurred in one (1.6%) patient within five minutes of the device release, which could not be retrieved non-surgically. Size of the device used was either same or preferably 1-3 mm more than the balloon-stretched atrial septal defect diameter. Total procedure time was 40-90 (59 +/- 12.4) minutes and the fluoroscopy time was 12-30 (17.3 +/- 4.2) minutes. Immediate post-procedure and pre-discharge echocardiography in patients with successful deployment of the device revealed complete abolition of shunt in 61 (98.4%) and trivial residual shunt in one (1.6%) patient. No patient developed atrioventricular valve regurgitation or cardiac arrhythmias. Thus, atrial septal defect closure using self-expandable septal occluder is a safe and efficacious procedure requiring a short procedural time. There is full control in the system for proper positioning or repositioning of the device with excellent technical success rate even in cases with insufficient anterosuperior septal margin.


The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver disease.
The fatty acid translocase (FAT)/CD36 belongs to the class B scavenger receptor family. In addition to the known functions of CD36 in the uptake of oxidized low-density lipoprotein by macrophages and uptake of fatty acids by adipose tissues, skeletal muscle and heart, emerging evidence has pointed to an equally important function of CD36 in the uptake of fatty acids in the liver and the pathogenesis of fatty liver disease. Recent reports have also suggested CD36 as a shared transcriptional target of several ligand-sensing and lipogenic transcriptional factors, such as the aryl hydrocarbon receptor, and several nuclear hormone receptors, such as pregnane X receptor, liver X receptor and peroxisome proliferator activated receptor γ. Non-alcoholic fatty liver disease is common and medically significant, because it is closely related to metabolic syndrome and has a potential to progress into the more harmful non-alcoholic steatohepatitis. It is hoped that CD36 and their transcriptional regulators can represent novel therapeutic targets for the prevention and management of fatty liver disease.


Structural similarity of ghrelin derivatives to peptidyl growth hormone secretagogues.
Ghrelin is a 28-amino acid residue endogenous growth hormone secretagogue. Intensive investigations revealed that the N-terminus tetrapeptide, having octanoyl group at Ser(3), is the minimum active core. In this study, we further explored the structure-function relationships of the active N-terminus portion of ghrelin using a Ca(2+) mobilization assay. The smallest and most potent ghrelin derivative we have found so far is 5-aminopentanoyl-Ser(Octyl)-Phe-Leu-aminoethylamide, showing comparable activity to the natural molecule. In the process of modifying the active core, the ghrelin-derived short analogues emerged structurally close to peptidyl growth hormone secretagogues. The N-terminus modification suggested that Gly(1)-Ser(2) unit works as a spacer, forming adequate distance between N(alpha)-amino group and n-octanoyl group. Replacement of 3rd and 4th amino acid residues to D-isomer suggested that the N-terminal dipeptide contributes to shape the biologically active geometry by effecting conformation of residues in positions 3 and 4.


[The Schreber case and Freudian dynamic psychopathology of psychoses].
We examined the diversity of diagnoses for the Schreber case, which was documented in "Memoirs of My Nervous Illness". Although Schreber became widely known as a paranoiac (or schizophrenic) patient after the publication of Freud's paper in 1911, some psychiatrists who use the operational diagnostic system have regarded him as a case of depression (or mood disorder). At present, the diagnosis of the Schreber case is divided between schizophrenia and mood disorder, which is based on the 'Kraepelinian dichotomy'. Recently, this dichotomy has been criticized as an unreasonable one, and some aspects of mood disorders are being discussed as resulting from the same biological foundation as schizophrenia. Similarly, many psychoanalysts found the same libidinal disturbance of these disorders. From the Freudian dynamic viewpoint, we conclude that schizophrenia and endogenous mood disorders have the common pathway (libidinal disturbance) in their acute phase. The findings of our literature review indicate that Freudian dynamic and economic perspective can shed a new light on the endogenous psychoses.


Blood pressure power within frequency range approximately 0.4 Hz in rat conforms to self-similar scaling following spinal cord transection.
This study quantified the effect of interrupting the descending input to the sympathetic preganglionic neurons on the dynamic behavior of arterial blood pressure (BP) in the unanesthetized rat. BP was recorded for approximately 4-h intervals in six rats in the neurally intact state and in the same animals after complete spinal cord transection (SCT) between T(4) and T(5). In the intact state, power within the frequency range of 0.35-0.45 Hz was 1.53 +/- 0.38 mmHg(2)/Hz (mean +/- SD by fast Fourier transform). One week after SCT, power within this range decreased significantly (P < 0.05) to 0.43 +/- 0.62 mmHg(2)/Hz. To test for self-similarity before and after SCT, we analyzed data using a wavelet (i.e., functionally, a digital bandpass filter) tuned to be maximally sensitive to fluctuations with periods of approximately 2, 4, 8, 16, 32, or 64 s. In the control state, all fluctuations with periods of >/=4 s conformed to a "self-similar" (i.e., fractal) distribution. In marked contrast, the oscillations with a period of approximately 2 s (i.e., approximately 0.4 Hz) were significantly set apart from those at lower frequencies. One day and seven days after the complete SCT, however, the BP fluctuations at approximately 0.4 Hz now also conformed to the same self-similar behavior characteristic of the lower frequencies. We conclude that 1) an intact sympathetic nervous system endows that portion of the power spectrum centered around approximately 0.4 Hz with properties (e.g., a periodicity) that differ significantly from the self-similar behavior that characterizes the lower frequencies and 2) even within the relatively high frequency range at 0.4 Hz self-similarity is the "default" condition after sympathetic influences have been eliminated.


Cluster Analysis of Primary Care Physician Phenotypes for Electronic Health Record Use: Retrospective Cohort Study.
Electronic health records (EHRs) have become ubiquitous in US office-based physician practices. However, the different ways in which users engage with EHRs remain poorly characterized. The aim of this study is to explore EHR use phenotypes among ambulatory care physicians. In this retrospective cohort analysis, we applied affinity propagation, an unsupervised clustering machine learning technique, to identify EHR user types among primary care physicians. We identified 4 distinct phenotype clusters generalized across internal medicine, family medicine, and pediatrics specialties. Total EHR use varied for physicians in 2 clusters with above-average ratios of work outside of scheduled hours. This finding suggested that one cluster of physicians may have worked outside of scheduled hours out of necessity, whereas the other preferred ad hoc work hours. The two remaining clusters represented physicians with below-average EHR time and physicians who spend the largest proportion of their EHR time on documentation. These findings demonstrate the utility of cluster analysis for exploring EHR use phenotypes and may offer opportunities for interventions to improve interface design to better support users' needs.


[Naringenin may block RSV-induced mucous hypersecretion in A549 cell via JNK/AP-1 signaling pathway].
Naringenin has been reported to attenuate Mucin (MUC) 5AC secretion in many pathological models. Many stimuli activate MUC5AC expression through JNK/AP-1 signaling pathways. We hypothesized that naringenin may have inhibitory effects on mucous hypersecretion by modulating MUC5AC production and inhibiting JNK/AP-1 signaling pathways. The cell model of mucous hypersecretion was made by human lung adenocarcinoma epithelial (A549) cells stimulated by RSV. A549 cells were subcultured and then randomly divided into 7 groups, which were designated as group C (cell control group), groups R1-3 (cells were infected with RSV at the multiplication of infection (MOI) of 0. 5, 1. 0, 5. 0), groups N1-2 (cells infected with viruses in presence of Nar 30 - 100 mol/L), groups N3-4 (uninfected cells treated with Nar 30 - 100 µmol/L), group D (DMSO), group S (cells infected with viruses in presence of SP600125). After incubating for 24 hrs, the expression of MUC5AC at mRNA and protein level in the groups were determined by real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). The protein expression changes of JNK, p-JNK and AP-1 were measured by Western blotting. The expressions of MUC5AC protein and mRNA in all RSV infected groups were significantly higher than that in group C in a dose-dependent manner (all P <0. 05). Nar of 30 and 100 µmol/L significantly and dose-dependently decreased RSV-induced secretion of MUC5AC protein in cell supernatant and expression of MUC5AC mRNA (P <0. 05). The relative content of p-JNK, AP-l in R2 groups were 3. 31 ± 0. 34 and 1. 94 ± 0. 05. Theyfrweremtgnificanty increased as compared with group C (both 1. 00 ± 0. 00) (all P <0. 05). The levels of p-JNK in N2 and S groups were 2. 10 ± 0. 20. 27 and 1.±97 ± 0. 16. The levels of AP-1 in N2 and S groups were 1. 40 ± 0. 03, 1. 36 ± 0. 05. Nar and SP600125 led to a largest decrease in levels of p-JNK and AP-1 when compared with group R2 (P <0. 05). The MUC5AC protein in group R2 was (48. 19 ± 0. 47) µg/L. The protein expression of MUC5AC in group R2 was significantly higher than that in group C [(36. 67 ± 1. 50) g/L] with a statistically significant difference (P <0. 05). The protein expression of MUC5AC in groups N2 and S were(43. 17 ± 1. 06) µg/L, (44.±02 ± 0. 99) µg/L, Nar and SP600125 remarkably inhibited RSV-induced secretion of MUC5AC in supernatant of A549 cells (P < 0. 05). Naringenin might be able to block RSV-induced mucous


Efficient control of Japanese encephalitis virus in the central nervous system of infected pigs occurs in the absence of a pronounced inflammatory immune response.
Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia. JEV infection of mice and humans can lead to an uncontrolled inflammatory response in the central nervous system (CNS), resulting in a detrimental outcome. Pigs act as important amplification and reservoir hosts, and JEV infection of pigs is mostly subclinical. Information on virus spread in the CNS and immune responses controlling JEV infection in the CNS of pigs, however remains scarce. Nine-week-old pigs were inoculated intranasal or intradermal with a relevant dose of 105 TCID50 of JEV genotype 3 Nakayama strain. Clinical signs were assessed daily, and viral spread was followed by RT-qPCR. mRNA expression profiles were determined to study immune responses in the CNS. Besides a delay of 2 days to reach the peak viremia upon intranasal compared to intradermal inoculation, the overall virus spread via both inoculation routes was highly similar. JEV appearance in lymphoid and visceral organs was in line with a blood-borne JEV dissemination. JEV showed a particular tropism to the CNS but without the induction of neurological signs. JEV entry in the CNS probably occurred via different hematogenous and neuronal pathways, but replication in the brain was mostly efficiently suppressed and associated with a type I IFN-independent activation of OAS1 expression. In the olfactory bulb and thalamus, where JEV replication was not completely controlled by this mechanism, a short but strong induction of chemokine gene expression was detected. An increased IFNy expression was simultaneously observed, probably originating from infiltrating T cells, correlating with a fast suppression of JEV replication. The chemokine response was however not associated with the induction of a strong inflammatory response, nor was an induction of the NLRP3 inflammasome observed. These findings indicate that an adequate antiviral response and an attenuated inflammatory response contribute to a favorable outcome of JEV infection in pigs and help to explain the limited neurological disease compared to other hosts. We show that the NLRP3 inflammasome, a key mediator of neurologic disease in mice, is not upregulated in pigs, further supporting its important role in JEV infections.


Foreign bodies and caustic lesions.
Foreign body ingestions, food bolus impactions, and caustic agent injuries are frequent but specific situations. Although most foreign bodies will naturally pass through the digestive tract, practitioners should recognize specific situations were endoscopic management is required. In such cases, timing and adequate equipment are critical. Endoscopic treatment is successful in about 95% of patients. Severe complications (including oesophageal perforations) are rare. Underlying diseases (including eosinophilic oesophagitis) must be investigated after food bolus impaction. Accidental or suicidal ingestion of corrosive agents may result in severe upper gastrointestinal tract injuries requiring a multidisciplinary approach including gastroenterologists, surgeons, otorhynolaryngologists, anaesthesiologists and psychiatrists. Treatment includes conservative management of patients with mild injuries, while patients with severe injuries undergo emergency surgical exploration. At distance of the ingestion episode, oesophageal reconstruction is required in patients who underwent oesophageal resection and in patients who developed oesophageal strictures that failed dilatation.


Two different pathogenetic mechanisms may play a role in acne and in hirsutism.
Acne is one of the most common skin disorders. Androgens are known to play an important and possibly central role. Androgens secreted from ovaries and adrenal glands (androstenedione, dehydroepiandrosterone and its sulphate, testosterone) and target tissue-produced androgens (testosterone and its 5 alpha-reduced metabolite, dihydrotestosterone) have been implicated. Although the sebaceous gland and the hair follicle form a single morphological entity, the pilosebaceous unit, acne and hirsutism do not always appear concomitantly, thus leading to the supposition that these two structures may have different degrees of sensitivity to similar androgenic stimulation. To determine whether acne and hirsutism are the clinical expression of a different androgen metabolism at target tissue levels we studied 90 randomly selected patients who came to our Out-patient Department for diagnosis and treatment during the last 2 years with isolated acne of mild to severe degree and 52 patients with idiopathic hirsutism without acne or history of acne. Twenty-four women without acne or hirsutism and without a history of endocrine disease were studied as controls. In both groups of patients, plasma levels of sex hormone binding globulin, of dihydrotestosterone, and of 3 alpha-androstanediol and of its glucuronide were evaluated. In all patients the percentage of free testosterone and the testosterone/sex hormone binding globulin ratio were also calculated. Patients with acne and those with isolated hirsutism showed significantly decreased sex hormone binding globulin plasma levels. The values of the percentage free testosterone and those of the testosterone/sex hormone binding globulin ratio were, on the contrary, higher with respect to the controls, although there were no statistically significant differences between the two groups. Significantly increased plasma levels of dihydrotestosterone with respect to the controls were observed in patients with acne or in those with hirsutism. However, while all patients with hirsutism showed increased plasma values of 3 alpha-androstanediol and its glucuronide, all patients with acne showed plasma levels within the normal range, independently of the precursor plasma levels. Our results demonstrate that dihydrotestosterone is further reduced to 3 alpha-androstanediol and its glucuronide only in hirsute patients but not in acne patients. These results suggest that dihydrotestosterone may undergo different metabolic pathways at skin levels and support the hypothesis that the two clinical manifestations may be the expression of the different metabolic fate of dihydrotestosterone itself. Moreover, our results demonstrate that 3 alpha-androstanediol and its glucuronide cannot be used as plasma markers of target-tissue produced androgens in all hyperandrogenic conditions.


¹H-MR spectroscopy of adult-onset autosomal dominant leukodystrophy with autonomic symptoms.
Adult-onset ADLD with autonomic symptoms is a rare disease with a clinical course somewhat similar to chronic progressive MS but with different imaging findings consisting of extensive white matter changes in the cerebrum and cerebellar peduncles. Patients usually present in the fourth to sixth decade with autonomic symptoms, manifesting later symptoms from the pyramidal tracts and ataxia. Here, we present magnetic resonance spectroscopy (MRS) findings in this disease. Fourteen subjects, from two non-related families, with genetic linkage to the disease were studied with magnetic resonance imaging and single-voxel MRS. Clinically, they ranged from asymptomatic to wheelchair-using. Their results were compared to those of age- and sex-matched healthy controls. One MRS was excluded due to suboptimal quality. The remaining 13 subjects manifested characteristic evidence of pathology on MRI, 11 of them exhibited extensive changes. The metabolite concentrations of total Cr, total Cho, and total NAA measured in millimolars, using internal water as a reference, were significantly lower in these 11 subjects compared to controls, and we found linear correlations between all these metabolite levels. When total Cr was used as a reference, we found no difference between subjects and controls. No lactate was detected. The decreased metabolite concentrations measured using internal water as a reference are most likely due to increased water content in the tissues, diluting all metabolites to a similar degree. This is also in agreement with the high signal intensity exhibited in the white matter on T2-weighted MR images and with the reported histopathological findings of vacuolated myelin.


Comparative DNA profiling, phytochemical investigation, and biological evaluation of two Ficus species growing in Egypt.
A comparison between two Ficus species, cultivated in Egypt, was carried out in this study. Their DNA analysis revealed that they are not closely related. The pharmacopoeial constants of the leaves showed higher total ash and acid insoluble ash in F. lyrata than in F. platypoda. The other parameters were close in both species. Preliminary phytochemical screening revealed the presence of carbohydrate and/or glycosides, tannins, flavonoids, sterols, and triterpenes in their leaves and was detected in traces in their stems. Saponification of n-hexane extract of the leaves yielded 46% and 74.8% for the unsaponifiable matters and 20% and 15% for the fatty acids for F. platypoda and F. lyrata, respectively. n-Docosane (21.69%) and n-heptacosane (33.77%) were the major hydrocarbons in F. platypoda and F. lyrata, respectively. b-Sitosterol was the main sterol, palmitic (22.07%) and carboceric (35.72%) acids were the major identified saturated fatty acids in both species, while linoleic acid was the main unsaturated fatty acid (18.66% and 16.7%) in both species, respectively. The acute toxicity study revealed that the two species were safe up to 2 g/kg. The antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and pyrogallol as the standard was more significant for F. platypoda (232.6 μg/ml) than for F. lyrata, (790.9 μg/ml). The oral antihyperglycemic activity in diabetic rats using alloxan revealed that the 80% ethanolic extract of the leaves of F. platypoda was more active than that of the leaves of F. lyrata in decreasing the blood glucose level at 200 mg/kg/day (107.9 ± 5.817, 127.2 ± 4.359) and 400 mg/kg/day (64.11 ± 4.358, 127.7 ± 6.889), respectively, when compared with the diabetic control gliclazide (172.3 ± 2.089). The results of this study provide evidence that the two Ficus species have antioxidant and antihyperglycemic activity, in the order F. platypoda and then F. lyrata.


Localized ovarian cancer in the elderly. The Gynecologic Oncology Group experience.
The appropriate therapy for patients with localized (FIGO Stage I and II) ovarian cancer has been poorly defined for all age groups and particularly for the elderly. Few prospective randomized comparisons of adjuvant therapy after careful surgical staging have been performed. The Gynecologic Oncology Group (GOG) has performed a series of trials testing adjuvant treatment in carefully staged patients with early-stage ovarian cancer. Early trials included few elderly patients but the most recent trial (GOG 95) included 18% over the age of 65 years. Comprehensive surgical staging defined by protocol is performed before randomization. Patients with predefined stages and histologies are included and the patients are randomized prospectively to receive either intraperitoneal phosphorus-32 or three monthly cycles of cyclophosphamide and cisplatin. Assessment of the value of this adjuvant therapy will depend on survival, disease-free survival, and relapse pattern differences between the two adjuvant therapies. This is an ongoing clinical trial and insufficient numbers of patients have been randomized for definitive conclusions. There have been seven recurrences on both arms of the trial with a median time to recurrence of 14 months. There currently are no significant age differences between relapsed patients and disease-free patients. At this point, 12 elderly patients have been randomized to each of the arms of therapy. Although no apparent survival differences exist for elderly patients in the most recent adjuvant chemotherapy trial of early ovarian cancer, the number of patients with cancer randomized and follow-up are insufficient to establish such a difference. Currently there is no evidence that elderly patients display a significant difference in relapse frequency or pattern.


Evaluation of gentamicin premixed admixtures: cost and clinical utility.
An objective of this study was to evaluate the cost effectiveness of employing gentamicin premixed admixtures compared to using exact, individualized compounded doses. Gentamicin use and waste data were collected over a 2-month period. Annualized institutional savings (300 beds) were projected to be $8,802. A second objective was to compare predicted to measured peak and trough serum gentamicin concentrations when premixed admixtures are used (rounding off computer generated doses to the nearest 10 mg) and when individually compounded exact doses are delivered. Twenty adults were randomized to receive premixed or compounded doses. Blood levels drawn at steady state were compared to predicted levels for the delivered dose. Differences between measured and predicted levels were not significant by performance of an independent t test on the mean square prediction errors. We conclude that it is cost effective and clinically valid to employ premixed intravenous admixtures in a large teaching hospital.


Unintentional, nonfatal firearm-related injuries. A preventable public health burden.
To describe the magnitude and characteristics of unintentional, nonfatal firearm-related injuries treated in US hospital emergency departments. Data were obtained from medical records for all firearm-related injury cases identified using the National Electronic Injury Surveillance System (NEISS) from June 1, 1992, through May 31, 1994. We report on cases classified as unintentional gunshot wounds. NEISS comprises 91 hospitals that are a stratified probability sample of all hospitals in the United States and its territories that have at least 6 beds and provide 24-hour emergency service. Number of and population rates for unintentional, nonfatal firearm-related injuries. An estimated 34 485 (95% confidence interval [CI], 25 225-43 745) persons (6.7 per 100 000 population; 95% CI, 4.9-8.5) were treated for unintentional, nonfatal firearm-related injuries in US emergency departments during the 2-year study period. The majority of patients were male (87%) and aged 15 to 34 years (61%); 38% required hospitalization. Injuries were most often to an extremity (73%), were self-inflicted (70%), involved a handgun (57%), and resulted during common gun-related activities. Further development of effective interventions are needed to reduce the risk of injury from unintentional discharge of a firearm during routine gun-handling practices by those who own and use firearms. These injuries often occur during common gun-related activities such as gun cleaning, loading/unloading, hunting, target shooting, and showing, handling, or carrying. Studies are needed to evaluate the efficacy of existing gun safety training courses and assess the potential role of various gun safety devices (eg, trigger locks and loading indicators) in future prevention strategies.


[Clinical significance of thrombocytopenia associated with hemorrhagic cerebrovascular diseases].
We investigated the clinical significance of thrombocytopenia (platelet counts less than 10 x 10(4)/mm3) associated with hemorrhagic cerebrovascular disease. This study was conducted in 96 patients suffering from hemorrhagic cerebrovascular diseases. We divided the clinical course into 3 stages: acute (from the 1st to 7th day), subacute (8th-21st day) and chronic (after the 22nd day). The average age of the patients with thrombocytopenia (TCP) was 60.6 years old. TCP was more frequent in men (81.3%) than in women (18.7%). TCP developed in 18.6% (8/43) of patients with subarachnoid hemorrhage (SAH) and in 15.1% (8/53) of those with intracerebral hemorrhage (ICH). Among the patients with SAH, four were in the acute stage, three in the subacute stage and two in the chronic stage. TCP due to SAH was more likely to develop in the acute and/or subacute stage. TCP due to SAH showed two peak appearances: the first was within 24 hours (n = 3), and the second was around 10 days after onset (n = 3). The cause of TCP in its late peak appearance was presumed to be the consumption of platelets due to microembolism induced by vasospasm and/or hemodilution therapy. Among patients with ICH, five cases were in the acute stage, three in the subacute stage and two in the chronic stage. TCP due to ICH was more likely to develop in the acute stage. Fifty percent (4/8) of the patients with ICH had TCP on admission. This data suggested that TCP was possibly a cause or an inducer for ICH.(ABSTRACT TRUNCATED AT 250 WORDS)


Differentiation of human olfactory mucosa mesenchymal stem cells into photoreceptor cells in vitro.
To investigate whether the human olfactory mucosa mesenchymal stem cells (OM-MSCs) can differentiate into photoreceptor cells in vitro. Through the olfactory mucosa adherent method, olfactory mucosa was isolated, cultured and identified in vitro among mesenchymal stem cells. The cell surface markers were analyzed by flow cytometry, induced to differentiate into retinal photoreceptor cells in vitro, and the expression of rhodopsin was observed and identified by Immunofluorescence and Western blot methods. OM-MSCs from human were spindle cell-based, and showing radial colony arrangement. OM-MSCs were negative for CD34, CD45 and CD105, but positive for CD73 and CD90. Following induction, a strong positive reaction was produced by photoreceptor specific marker rhodopsin in the cells. This novel finding demonstrates that OM-MSCs can be cultured and expanded in vitro. They possess biological characteristics of mesenchymal stem cells, and have the ability to be induced into retinal cells.


Explorations on Growth of Blue-Green-Yellow-Red InGaN Quantum Dots by Plasma-Assisted Molecular Beam Epitaxy.
Self-assembled growth of blue-green-yellow-red InGaN quantum dots (QDs) on GaN templates using plasma-assisted molecular beam epitaxy were investigated. We concluded that growth conditions, including small N2 flow and high growth temperature are beneficial to the formation of InGaN QDs and improve the crystal quality. The lower In/Ga flux ratio and lower growth temperature are favorable for the formation of QDs of long emission wavelength. Moreover, the nitrogen modulation epitaxy method can extend the wavelength of QDs from green to red. As a result, visible light emissions from 460 nm to 622 nm have been achieved. Furthermore, a 505 nm green light-emitting diode (LED) based on InGaN/GaN MQDs was prepared. The LED has a low external quantum efficiency of 0.14% and shows an efficiency droop with increasing injection current. However, electroluminescence spectra exhibited a strong wavelength stability, with a negligible shift of less than 1.0 nm as injection current density increased from 8 A/cm2 to 160 A/cm2, owing to the screening of polarization-related electric field in QDs.


Occupation and lung cancer mortality in a nationally representative U.S. Cohort: The National Health Interview Survey (NHIS).
The objective of this study was to assess the risk of lung cancer mortality in a nationally representative sample of U.S. workers by occupation. National Death Index linkage identified 1812 lung cancer deaths among 143,863 workers who participated in the 1987, 1988, and 1990-1994 National Health Interview Surveys. Current and former smoking status was predictive of lung cancer mortality (hazard ratio [HR] = 15.1 and 3.8, respectively). Occupations with significantly higher risk for age- and smoking-adjusted lung cancer mortality included heating/air/refrigeration mechanics (HR = 3.0); not specified mechanics and repairers (HR = 2.8); financial records processing occupations (HR = 1.8); freight, stock, and materials handlers (HR = 1.5); and precision production occupations (HR = 1.4). Although tobacco use continues to be the single most important risk factor for lung cancer mortality, occupational exposure to lung carcinogens should be targeted as well to further reduce the burden of lung cancer.


Gas exchange during exercise in mild chronic obstructive pulmonary disease. Correlation with lung structure.
To investigate whether or not the pathologic features in the lungs of patients with chronic obstructive pulmonary disease (COPD) are related to the gas exchange response during exercise, we studied 17 patients (15 men, two women) with mild-to-moderate airflow obstruction (FEV1/FVC ratio, 59 +/- 3%), undergoing resective lung surgery, at rest and during submaximal exercise (71 +/- 5% predicted VO2max). During exercise, arterial PO2 increased (from 81 +/- 3 to 86 +/- 3 mm Hg, p less than 0.05) as a result of an overall improvement in VA/Q relationships. This improvement included an increase in the mean VA/Q ratios of both ventilation and blood flow distributions, and a more homogeneous ventilation distribution (logSD V, from 0.66 +/- 0.06 to 0.50 +/- 0.03; p less than 0.01; normal value, less than or equal to 0.6). The morphologic evaluation of the resected specimens disclosed a moderate degree of emphysema (emphysema score, 16 +/- 4) and mild abnormalities in membranous bronchioles (total pathology score, 107 +/- 8). At rest, significant correlations were found between the severity of the pathologic findings and both the degree of hypoxemia and the extent of VA/Q mismatching. During exercise, no relationship between bronchiolar abnormalities and gas exchange measurements was observed, whereas the severity of emphysema was correlated with PaO2 (r = -0.54, p less than 0.05). Both the overall increase in and the more efficient distribution of ventilation accounted for the improvement in VA/Q distributions during exercise. These changes were more pronounced in patients with a greater degree of bronchiolar abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)


Tuberculosis in east timorese refugees: implications for health care needs in East Timor.
East Timorese refugees evacuated to Darwin, Australia, September 1999. Presentation of the process and results of tuberculosis (TB) screening in a previously unscreened refugee population. Screening for TB by clinical examination (all persons) and chest X-ray (CXR) (persons over 12 years of age and those of any age with respiratory symptoms) and sputum microscopy and mycobacterial culture (abnormal CXR). Seventy-six patients were diagnosed with TB (38 culture-positive for Mycobacterium tuberculosis, including 11 sputum smear-positive). Of 89 positive mycobacterial cultures, 51 were non-tuberculous mycobacteria (NTM). Of the M. tuberculosis isolates, 82.2% were fully sensitive, 17.2% were resistant to isoniazid and 8.6% were resistant to isoniazid and streptomycin. Fifty-three consecutively diagnosed patients with TB were HIV-negative. The TB burden in this population was very high (point prevalence of 542/100,000 for smear-positive and 2,060/100,000 for culture-positive cases). Rates of culture for NTM were also high. Information from this study assisted the implementation of a National TB Control Programme for East Timor in February 2000. The challenges for public health authorities in East Timor to provide a successful TB control programme are enormous. The apparently low prevalence of drug resistance and HIV co-infection in the population is encouraging.


Pirfenidone inhibits epidural scar fibroblast proliferation and differentiation by regulating TGF-β1-induced Smad-dependent and -independent pathways.
Epidural fibrosis causes serious complications in patients who have undergone laminectomy. Pirfenidone is an effective antifibrotic agent but its effect on epidural fibrosis remains unclear. In this study, we aimed to investigate the effect of pirfenidone on epidural fibrosis and to evaluate its mechanism of action on human epidural scar fibroblasts. In a rat model of laminectomy, the degree of epidural fibrosis was quantified via Rydell standard classification, histological analysis, and collagen density analyses. In cultured human epidural scar fibroblasts, cell proliferation was measured using a Cell Counting Kit-8 and EdU assay. Cell apoptosis was detected using Annexin V/propidium iodide staining, and cytotoxicity was evaluated via lactate dehydrogenase assay. Relative mRNA levels of α-smooth muscle actin (α-SMA) and collagen type I were analyzed using quantitative polymerase chain reaction. The protein expression of α-SMA and collagen type I and the phosphorylation status of Smad2, Smad3, protein kinase B (Akt), and p38 were determined via western blotting. Pirfenidone reduced epidural fibrosis by inhibiting fibroblast proliferation and suppressing collagen formation in rats. It also inhibited human epidural scar fibroblast proliferation with no cytotoxic or apoptotic effects. Pirfenidone inhibited fibroblast differentiation by decreasing TGF-β1-induced transcriptional and translational expression of α-SMA. It inhibited TGF-β1-induced phosphorylation of Smad2, Smad3, Akt, and p38. This study suggests that topical application of pirfenidone could reduce epidural scar adhesion after laminectomy, and that its mechanism of action may be the inhibition of TGF-β1-induced epidural scar fibroblast proliferation and differentiation into myofibroblasts through the attenuation of TGF-β1-induced Smad-dependent and -independent pathways.


Effect of neurotropin on hyperalgesia induced by prostaglandin E2, naloxone, melatonin and dark condition in mice.
Subcutaneous injection of formaldehyde into mouse hind paw elicited pain responses consisting of licking or biting of the paw, which were observed biphasically. The first and second phases were enhanced by melatonin and melatonin, naloxone, prostaglandin E2, respectively. Mice kept in the dark also exhibited hyperalgesic response. When neurotropin was injected intraperitoneally 30 min prior to those treatments, hyperalgesia was suppressed to the control level. Aspirin inhibited only the second hyperalgesic phase.


The auditory brain stem response reliably predicts hearing loss in graduates of a tertiary intensive care nursery.
Babies (N = 642) were tested for auditory disorder, using the auditory brain stem response (ABR), at the time of their discharge from a tertiary intensive care nursery (ICN). Of those with ABR threshold elevation in one or both ears (N = 97), 61% (N = 59) were retested some months later by a battery of audiological tests; 21 (N = 3.3% of the 642) suffered binaural peripheral loss and 11 (1.7%) now wear hearing aids. These new data, when combined with similar data previously reported from the same ICN, yield a sample of 1613 babies examined during a 5.8-year period from which these conclusions emerge: (1) About 16% of our ICN babies leave the hospital with reduced sensitivity in one or both ears; (2) the hearing deficiency is permanent for 8 to 10%; (3) the loss is sensorineural, bilateral, and so severe for about 4% that hearing aids will be required to optimize their language and psychosocial development. Use of the ABR procedure for neonatal hearing testing is the target of several criticisms: it is being applied too early in life; its predictions about permanent hearing loss are unacceptably inaccurate; or/and it is too costly. We discuss these and still other objections that have been raised.


Optical clock with ultracold neutral atoms.
We demonstrate how to realize an optical clock with neutral atoms that is competitive to the currently best single ion optical clocks in accuracy and superior in stability. Using ultracold atoms in a Ca optical frequency standard, we show how to reduce the relative uncertainty to below 10(-15). We observed atom interferences for stabilization of the laser to the clock transition with a visibility of 0.36, which is 70% of the ultimate limit achievable with atoms at rest. A novel scheme was applied to detect these atom interferences with the prospect to reach the quantum projection noise limit at an exceptional low instability of 4 x 10(-17) in 1 s.


Riluzole attenuates glutamatergic tone and cognitive decline in AβPP/PS1 mice.
We have previously demonstrated hippocampal hyperglutamatergic signaling occurs prior to plaque accumulation in AβPP/PS1 mice. Here, we evaluate 2-Amino-6-(trifluoromethoxy) benzothiazole (riluzole) as an early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to substantial Beta amyloid (Aβ) plaque accumulation and cognitive decline. Male AβPP/PS1 mice, a model of progressive cerebral amyloidosis, were treated with riluzole from 2-6 months of age. Morris water maze, in vivo electrochemistry, and immunofluorescence were performed to assess cognition, glutamatergic neurotransmission, and pathology, respectively, at 12 months. Four months of prodromal riluzole treatment in AβPP/PS1 mice resulted in long-lasting procognitive effects and attenuated glutamatergic tone that was observed six months after discontinuing riluzole treatment. Riluzole-treated AβPP/PS1 mice had significant improvement in long-term memory compared to vehicle-treated AβPP/PS1 mice that was similar to normal aging C57BL/6J control mice. Furthermore, basal glutamate concentration and evoked-glutamate release levels, which were elevated in vehicle-treated AβPP/PS1 mice, were restored to levels observed in age-matched C57BL/6J mice in AβPP/PS1 mice receiving prodromal riluzole treatment. Aβ plaque accumulation was not altered with riluzole treatment. This study supports that interventions targeting the glutamatergic system during the early stages of AD progression have long-term effects on disease outcome, and importantly may prevent cognitive decline. Our observations provide preclinical support for targeting glutamate neurotransmission in patients at risk for developing AD. Read the Editorial Highlight for this article on page 399.


[What Should (Future) GPs Learn in Surgery?].
Surgical diseases are often primarily seen and initially treated as well as further patient care is organised in clinical practice by a general practitioner (GP). During postoperative time periods, GPs do have to i) ensure the surgical treatment success, ii) support reintegration of surgically pretreated patients within their daily and professional life as well as iii) coordinate follow-up care. Therefore, it is indicated for residents in general practice/family medicine to spend a certain time period of approximately 6 months at a surgical department of an outpatient clinic and/or hospital. A selective literature search was undertaken on the required surgical knowledge, abilities, skills and expertise that need to be achieved by residents of general practice/family medicine or, respectively, future GPs and that are listed within national regulations on further education, recommendations of professional groups as well as documents and data for preparation of exams. Surgical contents during residency in general practice/family medicine comprise far more than "small surgery" only. Requirements of regulations on specialised medical training for a temporary surgical mentor/supervisor and "trainees" provide orientation for the development of an "ideal" surgical rotation for future GPs.


[Requests for residency permits due to medical reasons from foreigners in the Val-d'Oise county between 1999 and 2003].
The requests for residence permits from foreigners who wish to remain in France for health reasons are submitted for review to the county public health medical officer. This article reports on the quantitative and qualitative evolution and progression of these requests in a county located near Paris. The number of requests has drastically increased, from 152 in 1999 to 1,823 in the year 2003. The majority of the applicants were women and individuals from sub-Saharan Africa. HIV infection was the most frequent reason cited for the submission of requests, but its relative proportion has decreased over time from 25% in 1999 to 15% of overall requests made in the year 2003, which is then followed by diabetes (8% of all requests), hypertension (5%), and tuberculosis (4%). The decision handed down from the authorities was favourable for residence based on the need for healthcare in 74% of the cases. The health status of the illegal immigrants remains difficult to determine and systematically track; therefore, the applications for residency granted on medical grounds serve as a practical and efficient means to assess and map the existing situation.


Quantitative analysis of dental porcelain surfaces following different treatments: correlation between parameters obtained by a surface profiling instrument.
This investigation compared, by quantitative analysis, the surface roughness of dental porcelain submitted to three different treatments (glaze, trimming and polishing), utilizing a surface profiling instrument. The parameters Ra (median roughness), Rz (median of the maximum profile heights of five sample lengths), Rpm (median of the maximum profile heights related to the median line of five sample lengths), Pc (peak count per centimeter) and Rpm/Rz (proportional parameter) were evaluated. In addition, the correlation between Ra and the other parameters was analyzed. Based on the results obtained, it was seen that the Ra parameter did not present any correlation with the other parameters in some of the situations evaluated. This demonstrates that complementation of the measurement with other parameters is always necessary, providing a better evaluation of the functional properties of a surface.


Mechanical loading by fluid shear is sufficient to alter the cytoskeletal composition of osteoblastic cells.
Many structural modifications have been observed as a part of the cellular response to mechanical loading in a variety of cell types. Although changes in morphology and cytoskeletal rearrangement have been widely reported, few studies have investigated the change in cytoskeletal composition. Measuring how the amounts of specific structural proteins in the cytoskeleton change in response to mechanical loading will help to elucidate cellular mechanisms of functional adaptation to the applied forces. Therefore, the overall hypothesis of this study was that osteoblasts would respond to fluid shear stress by altering the amount of specific cross-linking proteins in the composition of the cytoskeleton. Mouse osteoblast cell line MC3T3-E1 and human fetal osteoblasts (hFOB) were exposed to 2 Pa of steady fluid shear for 2 h in a parallel plate flow chamber, and then the amount of actin, vimentin, alpha-actinin, filamin, and talin in the cytoskeleton was measured using Western blot analyses. After mechanical loading, there was no change in the amount of actin monomers in the cytoskeleton, but the cross-linking proteins alpha-actinin and filamin that cofractionated with the cytoskeleton increased by 29% (P<0.01) and 18% (P<0.02), respectively. Localization of the cross-linking proteins by fluorescent microscopy revealed that they were more widely distributed throughout the cell after exposure to fluid shear. The amount of vimentin in the cytoskeleton also increased by 15% (P<0.01). These results indicate that osteoblasts responded to mechanical loading by altering the cytoskeletal composition, which included an increase in specific proteins that would likely enhance the mechanical resistance of the cytoskeleton.


Quality of life: a concept analysis.
Quality of life (QOL) is a phrase which was first used shortly after the Second World War and has, since then, been overused and infrequently defined. A concept analysis of QOL is presented to clarify the concept for further use. The process for concept analysis developed by Walker & Avant is employed. Quality of life is found to be very complex, and it is hoped that this analysis will stimulate thought and further nursing research into what QOL means in the health care context.


Use of multidetector computed tomography in the assessment of dogs with pericardial effusion.
Contrast-enhanced multidetector computed tomography (MDCT) allows high spatial and temporal resolution imaging of cardiac, thoracic, and abdominal structures. Accurate determination of the cause of pericardial effusion (PE) is essential to providing appropriate treatment and prognosis. Echocardiography and pericardial fluid analysis may not differentiate between causes of PE and cannot identify extracardiac metastasis. Describe the thoracic and abdominal MDCT findings and evaluate the utility of MDCT to differentiate between neoplastic and nonneoplastic causes of PE in dogs. Eleven client-owned dogs with PE diagnosed by echocardiography. Prospective observational study. Transthoracic echocardiography (TTE), 3-view thoracic radiography, and contrast-enhanced thoracic and abdominal MDCT images were evaluated for the presence of cardiac masses, pulmonary metastases, and abdominal masses. Histopathology in 5 dogs and survival analysis in all dogs were evaluated. A neoplastic cause was identified in 6/11 dogs and a nonneoplastic cause was identified in 5/11. Cardiac MDCT findings were consistent with TTE findings in all dogs with right atrial (5/5) and heart base masses (1/1). Pulmonary metastases were identified in 1/11 dogs by thoracic radiography and in 2/11 dogs by MDCT. MDCT identified splenic or hepatic lesions consistent with neoplasia in 6/11 and 5/11 dogs, respectively. Focal MDCT pericardial changes at the pericardiocentesis site were noted in 3/11 dogs. Multidetector computed tomography did not improve the detection of cardiac masses in dogs with PE over echocardiography. The benefit of MDCT was primarily in the detection of pulmonary metastases and extracardiac lesions using a single imaging modality.


Silver nanoparticles/montmorillonite composites prepared using nitrating reagent at water and glycerol.
Three procedures (P) were applied to prepare silver nanoparticles on natural Ca-montmorillonite (MT). The intercalation of the montmorillonite with silver nitrate in aqueous solution (P1), the intercalation of the montmorillonite with silver nitrate in glycerol (P2) and the successive combination of both P1 and P2 methods resulted to P3 method. X-ray powder diffraction (XRD), high-resolution transmission electron microscopy (HRTEM) and Fourier Transform Infrared (FTIR) spectroscopy and the molecular modeling were employed to characterize silver nanoparticles and montmorillonite nanocomposite. The P1 produced MT-1 composite with 2.3 wt% Ag and the partially collapsed layered structure. Nanoparticles of silver larger than 20 nm with a lot of planar defects were randomly distributed on the MT-1 surface; nanoparticles smaller than 20 nm were oriented to the montmorillonite substrate. The MT-2 composite from P2 contained only 1 wt% of Ag. The molecular simulation model of MT-2 showed the interlayer space with the exchangeable cations and metallic silver atoms arrangement within the glycerol bilayer. The P3 produced composite MT-3 that contained 2.4 wt% Ag. The nanoparticles > 20 nm size had a well-defined geometry, very small nanoparticles were amorphous. The modeled structure showed the exchangeable cations, Ag+ and Ag0 located close to the silicate layers and monolayer of glycerol molecules in the interlayer space.


White matter changes and late-life depressive symptoms: longitudinal study.
Evidence from cross-sectional studies suggests a link between cerebral age-related white matter changes and depressive symptoms in older people, although the temporal association remains unclear. To investigate age-related white matter changes on magnetic resonance imaging (MRI) as an independent predictor of depressive symptoms at 1 year after controlling for known confounders. In a pan-European multicentre study of 639 older adults without significant disability, MRI white matter changes and demographic and clinical variables, including cognitive scores, quality of life, disability and depressive symptoms, were assessed at baseline. Clinical assessments were repeated at 1 year. Using logistic regression analysis, severity of white matter changes was shown to independently and significantly predict depressive symptoms at 1 year after controlling for baseline depressive symptoms, quality of life and worsening disability (P<0.01). White matter changes pre-date and are associated with the development of depressive symptoms. This has implications for treatment and prevention of depression in later life.