The safety and efficacy of cadaveric allografts and titanium cage as a fusion substitutes in pyogenic osteomyelitis.
The safety and efficacy of various fusion substitutes in pyogenic osteomyelitis has not been investigated. We evaluated and compared the cadaveric allograft and titanium cages used to reconstruct, maintain alignment and achieve fusion in the management of pyogenic spinal infection. There were 33 patients with pyogenic osteomyelitis underwent fusion in this study. Fifteen of the 33 patients were operated on by fusion with allografts (cadaveric patella bones) and 18 of those were operated with titanium mesh cages filled with autologous cancellous iliac bone. After the affected disc and vertebral body resection with pus drainage, cadaveric allograft or titanium cages were inserted into the resected space. Posterior transpedicular screw fixation and rod compression in resected space, where cadaveric allograft or titanium cages were inserted, was performed to prevent the malposition in all patients except in 1 case. Recurrent infection was identified by serial erythrocyte sedimentation rate and cross reactive protein follow-up. Osseous union and recurred infection available at a minimum of 2 years following operation was identified. The amount of kyphosis correction and the subsidence were measured radiographically. Spinal fusion was achieved in 29 of 33 patients. In the cadaveric allograft group, 93.3% of patient (14 of 15) showed the osseous union while 83.3% of patient (15 of 18) in the titanium cage group showed union. Subsidence was noted in 12 of the patients. Twelve patients (36.3%) showed unsettling amounts of subsidence postoperatively whereas 46.6% of patients in the cadaveric allograft group and 37.7% of patients in the titanium cage group showed similar subsidence, respectively. There were statistical difference in the fusion rate (p=0.397) and subsidence rate (p=0.276) between the two groups. There was significant statistical difference in the postoperative improvement of segmental kyphosis between the two groups (p=0.022), that is the improvement in sagittal alignment was greater in the titanium cage group than in the cadaveric allograft group. There was no case of recurred infection. The cadaveric allograft and titanium cages are effective and safe in restoring and maintaining sagittal plane alignment without increased incidence in infection recurrence in pyogenic osteomyelitis. The postoperative improvement of segmental kyphosis was better in the cage group.


DNA light-strand preferential recognition of human mitochondria transcription termination factor mTERF.
Transcription termination of the human mitochondrial genome requires specific binding to termination factor mTERF. In this study, mTERF was produced in E. coli and purified by two-step chromatography. mTERF-binding DNA sequences were isolated from a pool of randomized sequences by the repeated selection of bound sequences by gel-mobility shift assay and polymerase chain reaction. Sequencing and comparison of the 23 isolated clones revealed a 16-bp consensus sequence of 5\'-GTGTGGCA GANCCNGG-3\' in the light-strand (underlined residues were absolutely conserved), which nicely matched the genomic 13-bp terminator sequence 5\'-TGGCAGAGCCC GG-3\'. Moreover, mTERF binding assays of heteroduplex and single-stranded DNAs showed mTERF recognized the light strand in preference to the heavy strand. The preferential binding of mTERF with the light-strand may explain its distinct orientation-dependent termination activity.


Atopic dermatitis endotypes: knowledge for personalized medicine.
Endotypes are clinically relevant phenotypes that can be explained by molecular mechanisms, and are defined to predict the development, progression, prognosis and responses to treatment on the individual level. This review summarizes atopic dermatitis phenotypes, endotypes and their potential application for personalized medicine. Atopic dermatitis can be classified into several phenotypes according to disease courses that likely have common pathophysiology. The genotype is important to define endotypes, but the value of genotype alone remains somewhat limited in most atopic dermatitis patients. Recent studies have demonstrated that atopic dermatitis phenotypes according to ethnicity or age can be classified into endotypes based on the dominant immunologic markers, that is TH1/TH2/TH17/TH22 cells. Newly developed biologic agents targeting specific cytokines show therapeutic potential in a personalized medicine approach. Cytokine-based endotypes in different age groups or ethnic groups have contributed to expanding our understanding of atopic dermatitis. Recent biologics or small molecules can be used for more personalized treatment of atopic dermatitis. Further research using integrated multiomic analysis is needed to define a more detailed classification of endotypes and provide endotype-driven targeted therapies for personalized medicine.


Surgical solution of selective epitympanic dysventilation syndrome
The selective epitympanic dysventilation syndrome is a new theory of the cholesteatoma formation, the description of which was allowed by a minimally invasive surgical technique – the transcanal endoscopic ear surgery – some years ago. The transcanal endoscopic ear surgery provided the possibility of a certain amount of detailed anatomical knowledge to identify the new factor behind this process, namely obstruction of the ventilation pathways of the middle ear. Our goal was to draw the ear surgeons' attention to this clinical picture as cholesteatoma development and subsequent worsening of the quality of life caused by ear discharge and conductive hearing loss may be reversible or preventable. We make the syndrome more understandable by using our own anatomical drawings. In this paper, the authors present a case of selective epitympanic dysventilation syndrome, and emphasize the importance of recognition and the endoscopic ear surgical treatment as well as review the international literature.


[The influence of hyperglycemia on functions of endothelial progenitor cells].
The isolation of endothelial progenitor cells changed our understanding of adult blood vessel formation. Recent studies have proven that EPCs functionally contribute to neovasculogenesis and reendothelization of damage blood vessels. It has been shown that patients with diabetes mellitus have decreased numbers of EPCs with impaired activities important to growth of blood vessels. It has been demonstrated that hypoglycemia cause abnormalities in EPCs proliferation, differentiation, adhesion and migration.


Thermally Stable and Reusable Ceramic Encapsulated and Cross-Linked CalB Enzyme Particles for Rapid Hydrolysis and Esterification.
Candida antarctica lipase B (CalB) enzyme was encapsulated and cross-linked by silica matrix to enhance its thermal stability and reusability, and demonstrated an enzymatic ability for rapid hydrolysis and esterification. Silica encapsulated CalB particles (Si-E-CPs) and silica cross-linked CalB particles (Si-CL-CPs) were prepared as a function of TEOS concentration. The particle size analysis, thermal stability, catalytic activity in different pHs, and reusability of Si-E-CPs and Si-CL-CPs were demonstrated. Furthermore, the determination of the CalB enzyme in Si-E-CPs and Si-CL-CPs was achieved by Bradford assay and TGA analysis. Enzymatic hydrolysis was performed against the p-nitrophenyl butyrate and the catalytic parameters (Km, Vmax, and Kcat) were calculated by the Michaelis-Menten equation and a Lineweaver-Burk plot. Moreover, enzymatic synthesis for benzyl benzoate was demonstrated by esterification with an acyl donor of benzoic acid and two acyl donors of benzoic anhydride. Although the conversion efficiency of Si-CL-CPs was not much higher than that of native CalB, it has an efficiency of 91% compared to native CalB and is expected to be very useful because it has high thermal and pH stability and excellent reusability.


Decree of 12 December 1983.
This Decree, which came into force on 26 March 1984, makes the following changes in the Civil Code of the Federal District of Mexico: 1) nonmarital life partners have a right to inherit from one another if they have lived together for five years or have common children; 2) such life partners are responsible for the support of each other; 3) marriage may be dissolved on a no fault basis after two years' marriage; 4) the custody of children upon divorce is to be determined on the basis of what is best for the child, without consideration of which spouse is at fault; 5) upon divorce, the wife has the right to support for a period equal to the length of the marriage if her own income is insufficient to support herself and she has not entered into any marital or similar relationship; and 6) upon divorce, the husband has the same right if he is unable to work and his own income is not sufficient to support himself.


WT1 expression in the female genital tract.
The Wilms tumor gene 1 (WT1) has been reported in normal tissues and many neoplasms of the female genital tract. This review discusses WT1 expression in the female genital tract and its potential utility in the differential diagnosis of neoplasms that occur at this location. WT1 is of value in the differential diagnosis of synchronous serous carcinomas arising in the ovary/fallopian tube/peritoneum and endometrium, as strong WT1 positivity in both tumors points toward an extrauterine origin. In addition, WT1 can be used to distinguish sex cord stromal tumors (WT1 positive) from endometrioid carcinomas (OECs). WT1 expression is not helpful in the differential diagnosis of ovarian serous carcinomas (OSCs) and transitional carcinomas, as both are typically positive and has limited value in the distinction of serous tumors arising in the ovary/fallopian tube/peritoneum from mesotheliomas. WT1 is also not helpful to differentiate small cell carcinoma of hypercalcemic type from juvenile granulosa cell tumor, a common diagnostic problem. Intra-abdominal desmoplastic round cell tumor reacts to WT1 (C-terminal) in contrast to all other tumors discussed which helps to separate this rare tumor from most other small round cell tumors that may involve, primarily or secondarily, the ovary with the exception of small cell carcinoma of hypercalcemic type that typically reacts with the N-terminal of WT1.


Effect of hoof boots and toe-extension shoes on the forelimb kinetics of horses during walking.
OBJECTIVE To determine and compare the effect of hoof boots (HBs) and shoes with a toe extension on stance duration, ground reaction force, and sole length in contact with the ground in nonlame horses during walking. ANIMALS 6 nonlame Standardbreds. PROCEDURES Force plate gait analyses of the forelimbs were performed while the horses were walking barefoot before manipulation of feet (baseline), while the horses were walking fitted with HBs, while the horses were walking shod with toe-extension shoes, and while the horses were walking barefoot after shoe removal. Horses underwent radiography of both forelimb feet to determine the sole length in contact with the ground when barefoot, wearing HBs, and shod with toe-extension shoes. Stance duration, ground reaction force, and sole length were compared among the various walking sessions. RESULTS Compared with baseline findings, stance duration increased significantly when horses were fitted with HBs (7%) or toe-extension shoes (5%). Peak forelimb ground reaction force was similar among walking sessions; however, time of braking force peak was significantly greater during the stance phase only when horses wore HBs. Also, the sole length in contact with the ground was significantly longer in horses fitted with HBs (14.3 cm) or shod with the toe-extension shoes (17.6 cm), compared with that for one of the barefoot hooves (12.7 cm). CONCLUSIONS AND CLINICAL RELEVANCE In nonlame horses, use of HBs prolonged the stance time and time of braking force peak, which is indicative of a slower deceleration phase during limb impact with the ground. Also, the use of HBs prolonged the deceleration phase of the stride and increased the sole length in contact with the ground.


Comparing Women's Contraceptive Preferences With Their Choices in 5 Urban Family Planning Clinics in Ghana.
Concern about contraceptive side effects is a common reason reported by women for not using contraception or discontinuing use. We sought to characterize women's preferences related to method characteristics and side effects and to examine whether their adopted method was consistent with their stated preferences. Between June 1, 2015, and August 31, 2015, we surveyed women attending 5 urban family planning clinics in Kumasi and Accra, Ghana, before and after their counseling sessions. All women attending these clinics were approached to gauge their interest and eligibility for inclusion. Before counseling, women were asked about desired method characteristics and bothersome and intolerable side effects. After counseling, women were asked about method adoption and the counseling received about side effects. We then used crosstabs to compare the side effects women were counseled to expect, as well as those they reported would be intolerable, with their adopted methods to determine consistency between women's preferences and choices. In total, 414 and 411 women completed the pre- and post-counseling surveys, respectively. The analysis sample consisted of 336 participants who adopted a method and were matched between the 2 surveys. The 3 most commonly chosen methods were the implant (n=135, 40.1%), injectables (n=109, 32.4%), and the intrauterine device (IUD) (n=52, 13.4%). The large majority (at least 87%) of method adopters chose a method that was well matched with their desired duration of effectiveness. Consistency between women's expressed intolerable side effects and their chosen methods was substantially lower: at least 70% of women choosing the implant, IUD, or injectables had stated they would stop using a method if they experienced those side effects that are in fact common with their respectively chosen methods. While 65.0% of those who adopted a method reported they were counseled to expect side effects, substantially less were counseled to expect the side effects common with use of their adopted method. Women's choice of contraceptive methods generally matched their stated preferences related to desired duration of effectiveness but not to potential side effects, and most women reported they were not counseled to expect the side effects common with use of their chosen method. Providers need to address potential side effects during counseling both to ensure women choose methods that will be a good fit with their desires and to reassure them that commonly experienced side effects are not harmful.


Expression of intermediate filament proteins in fetal and adult human kidney: modulations of intermediate filament patterns during development and in damaged tissue.
The expression of intermediate filament proteins, particularly individual cytokeratins (CKs), vimentin, and glial filament protein, was immunohistochemically investigated using frozen sections and Carnoy-fixed, paraffin-embedded tissue from normal fetal and adult human kidneys as well as from pathologically altered kidneys. In fetal kidneys, the co-expression of CKs and vimentin was detected in the visceral and parietal epithelium of the glomerulus, the proximal tubules, the thin loops of Henle, and the collecting ducts. In contrast, in the tubules of normal adult kidneys, the presence of vimentin and CKs was nearly always mutually exclusive. While CKs 8 and 18 were present in all tubular epithelia, CKs 19 and 7 each exhibited a distinctive distribution pattern, there being a striking alteration between positive and negative segments and, not infrequently, intratubular heterogeneities. In certain segments, particular cell types (e.g., "plica cells," intercalated cells) could thus be recognized. In tubular epithelia altered by various injurious conditions, novel or enhanced expression of vimentin, CK 19 and CK 7, and, less frequently, CK 17 and glial filament protein was noted in certain segments. The increase in intermediate filament protein expression in altered (particularly proximal) tubules appeared to parallel the reduction in the degree of differentiation. Vimentin was never detected in distal tubules. The present results reveal a considerable similarity between the intermediate filament patterns in non-neoplastic proximal tubules of fetal and damaged kidney tissue and those in clear-cell and chromophilic renal cell carcinomas. They also serve to illustrate that the analysis of both fetal development and reactive cell changes may significantly contribute to our understanding of differentiation phenomena in malignant tumors.


Radiofrequency ablation of a central renal tumor: protection of the collecting system with a retrograde cold dextrose pyeloperfusion technique.
Renal radiofrequency (RF) ablation therapy is a safe and effective therapy for small renal cell carcinoma. Although the risk of complications is low, the potential for ureteral or calyceal injury does increase in the case of a centrally located lesion. A retrograde cold dextrose pyeloperfusion technique was designed to protect the collecting system in a patient who underwent percutaneous RF ablation of a central tumor of the left kidney.


Characterization of a rice nuclear-encoded plastid RNA polymerase gene OsRpoTp.
We isolated and characterized two rice genes, OsRpoTp and OsRpoTm, that encode putative phage-type RNA polymerases. Predicted amino acid sequences showed high homology of these genes to known RpoT genes. A transient expression assay using green fluorescent protein indicated that the encoded proteins were localized to plastids and mitochondria, respectively. We demonstrated by reverse transcription-PCR experiments and immunoblot analysis that OsRpoTp expression occurred at an early stage of leaf development, prior to the transcript accumulation of the genes that were transcribed by the nuclear-encoded plastid RNA polymerase (NEP). Expression analyses of the chloroplast-deficient rice mutant, virescent-1, showed a discrepancy between OsRpoTp protein accumulation and the level of transcripts of NEP-transcribed genes. Our results suggest that NEP activation is regulated by a process after transcription, and is affected by the developmental state of chloroplast biogenesis.


Epileptic seizure detection using multiwavelet transform based approximate entropy and artificial neural networks.
Epilepsy is the most prevalent neurological disorder in humans after stroke. Recurrent seizure is the main characteristic of the epilepsy. Electroencephalogram (EEG) is the recording of brain electrical activity and it contains valuable information related to the different physiological states of the brain. Thus, EEG is considered an indispensable tool for diagnosing epilepsy in clinic applications. Since epileptic seizures occur irregularly and unpredictably, automatic seizure detection in EEG recordings is highly required. Multiwavelets, which contain several scaling and wavelet functions, offer orthogonality, symmetry and short support simultaneously, which is not possible for scalar wavelet. With these properties, recently multiwavelets have become promising in signal processing applications. Approximate entropy is a measure that quantifies the complexity or irregularity of the signal. This paper presents a novel method for automatic epileptic seizure detection, which uses approximate entropy features derived from multiwavelet transform and combines with an artificial neural network to classify the EEG signals regarding the existence or absence of seizure. To the best knowledge of the authors, there exists no similar work in the literature. A well-known public dataset was used to evaluate the proposed method. The high accuracy obtained for two different classification problems verified the success of the method.


Immunology of atopic eczema: overcoming the Th1/Th2 paradigm.
Atopic eczema (AE) is a challenge for modern medicine, because it is prevalent, severely affects quality of life of patients and their families, and causes high socioeconomic costs. The pathogenesis of AE is complex. While initial studies suggested a Th2 deviation as primary reason for the disease, numerous studies addressed a genetically predetermined impaired epidermal barrier as leading cause in a subgroup of patients. Recently, immune changes beyond the initial Th2 concept were defined in AE, with a role for specialized dendritic cells as well as newly identified T helper cell subsets such as Th17 and Th22 cells. Furthermore, trigger factors are expanded beyond classical Th2 allergens such as pollen or house dust mites to microbial products as well as self-antigens. This review pieces together our current understanding of immune as well as barrier abnormalities into the pathogenesis mosaic of AE.


Effect of topical ophthalmic latanoprost on intraocular pressure in normal horses.
The ocular effects of latanoprost ophthalmic solution were evaluated in two studies, with eight horses in each study. One eye of each horse was treated with latanoprost ophthalmic solution once daily for 5 days, and the opposite eye received a control solution of sterile eyewash. Intraocular pressure and pupillary diameter were measured daily for 5 days after treatment. Latanoprost had no significant effect on intraocular pressure or pupillary diameter in normal horse eyes compared with control eyes in these studies. Placement of an eyelid nerve block resulted in significantly lower intraocular pressure.


'In Short, We Will Deport You': Disrupted temporalities of migrants with HIV in Russia.
Migrants experience several challenges en route to or in their host country. Current legislation in Russia imposes a permanent ban on international migrants with HIV obtaining a residence permit in Russia. Using qualitative methodology, we conducted semi-structured interviews with 15 international migrants who have lived with HIV in Russia and 12 interviews with healthcare providers in Russia. With the help of Bonnington's temporal framework, the study finds that the HIV-positive status of migrants becomes a biographical event that interrupts their migration cycle, thereby leading to the disruption of their normal life course which results in 'short term planning' and instability. Although most people living with HIV face similar challenges, Russian law concerning international migrants living with HIV worsens their living experience in Russia. International migrants living with HIV further face social exclusion, serious stigma and discrimination. The results show that the country's demand for migrants with HIV to leave the country to reduce the spread of HIV in Russia is counterproductive: it does not mobilise heath-seeking behaviour among migrants. Therefore, such legislation has to be amended to encourage international migrants living with HIV to access adequate HIV services.


Phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 Is associated with the downregulation of peroxisome proliferator-activated receptor (PPAR)-γ during polymicrobial sepsis.
Peroxisome proliferator-activated receptor (PPAR)-γ is a ligand-activated transcription factor and regulates inflammation. Posttranslational modifications regulate the function of PPARγ, potentially affecting inflammation. PPARγ contains a mitogen-activated protein kinase (MAPK) site, and phosphorylation by extracellular signal-regulated kinase (ERK)-1/2 leads to inhibition of PPARγ. This study investigated the kinetics of PPARγ expression and activation in parenchymal and immune cells in sepsis using the MAPK/ERK kinase (MEK)-1 inhibitor, an upstream kinase of ERK1/2. Adult male Sprague Dawley rats were subjected to polymicrobial sepsis by cecal ligation and puncture. Rats received intraperitoneal injection of vehicle or the MEK1 inhibitor PD98059 (5 mg/kg) 30 min before cecal ligation and puncture. Rats were euthanized at 0, 1, 3, 6 and 18 h after cecal ligation and puncture. Control animals used were animals at time 0 h. Lung, plasma and peripheral blood mononuclear cells (PBMCs) were collected for biochemical assays. In vehicle-treated rats, polymicrobial sepsis resulted in significant lung injury. In the lung and PBMCs, nuclear levels of PPARγ were decreased and associated with an increase in phosphorylated PPARγ and phosphorylated ERK1/2 levels. Treatment with the MEK1 inhibitor increased the antiinflammatory plasma adipokine adiponectin, restored PPARγ expression in PBMCs and lung, and decreased lung injury. The inflammatory effects of sepsis cause changes in PPARγ expression and activation, in part, because of phosphorylation of PPARγ by ERK1/2. This phosphorylation can be reversed by ERK1/2 inhibition, thereby improving lung injury.


Tissue engineering of lung: the effect of extracellular matrix on the differentiation of embryonic stem cells to pneumocytes.
We have previously differentiated lung epithelium from human and murine embryonic stem cells (mESCs) and are now exploring the potential applications of these cells, including in the engineering of lung tissue constructs. In this study, we hypothesized that the differentiation and maintenance of lung epithelium derived from mESCs can be enhanced by extracellular matrix (ECM) proteins. Our established differentiation protocol was applied to mESCs grown on a range of ECMs: collagen I, laminin 332, fibronectin, Matrigel, and, as an experimental control, gelatin. The ECMs were coated onto tissue culture plastic (TCP) and poly-DL-lactic acid (PDLLA), a biodegradable polymer we have previously shown to support the growth of mature pneumocytes. Matrigel or Laminin-332 coating of either TCP or PDLLA film resulted in enhanced surfactant protein C gene expression in differentiating mESCs, a direct indication of the upregulation of lung epithelial differentiation. For each combination, changes in the contact angle and zeta potential of protein-coated TCP and PDLLA film confirmed protein adsorption. We conclude that the choice of the coating protein can greatly affect the differentiation of ESCs, and laminin-332-coated PDLLA provided an ECM-degradable scaffold combination that is suitable for engineering of lung tissue constructs.


The tumor suppressor protein HBP1 is a novel c-myc-binding protein that negatively regulates c-myc transcriptional activity.
c-Myc is an important transcription factor that regulates cellular proliferation, cell growth, and differentiation. A number of transcriptional co-factors for c-Myc have been described that have binding sites within highly conserved regions of the c-Myc transactivational domain (TAD). Given the importance of the c-Myc TAD, we set out to identify new proteins that interact with this region using a yeast two-hybrid assay. HBP1 was identified in our screen as a protein that interacts with full-length c-Myc but not a c-Myc mutant lacking the TAD. HBP1 is a transcriptional repressor and has been shown to negatively regulate the cell cycle. A correlation between HBP1 under-expression and breast cancer relapse has been described, suggesting that HBP1 may be an important tumor suppressor protein. We have found that HBP1 binds c-Myc in cells, and expression of HBP1 inhibits c-Myc transactivational activity at least partly by preventing c-Myc binding to target gene promoters. c-Myc binds to the C terminus of HBP1, a region lost in some breast tumors, and some HBP1 mutants found in breast cancer weakly interact with and/or no longer negatively regulate c-Myc. This work adds to our understanding of c-Myc regulation and mechanisms of tumor suppression by HBP1.


Periapical and endodontic status among 65-year-old Oslo-citizens.
This cross-sectional study aimed to investigate the prevalence of apical periodontitis (AP) and root-filled teeth in a 65-year-old population in Oslo, Norway, and to investigate associations of pathosis and endodontic treatment with selected individual risk indicators and technical quality of root fillings. A random sample of 450 65-year-olds in Oslo answered a questionnaire and underwent a clinical and radiological examination (52% men and 48% women). Periapical radiographs were taken of all root-filled teeth and of teeth with apical radiolucency, and periapical status was evaluated using the Periapical Index. Apex-to-filling distance and homogeneity were assessed for all root fillings. Analyses on individual level and tooth level were performed. The outcome variables were 'non-root-filled tooth with AP' ('untreated AP'), 'root-filled tooth', and 'root-filled tooth with AP'. The explanatory variables were gender, education, dental attendance pattern, smoking, remaining teeth (n), tooth group, and root filling quality. Chi-square test and logistic regression analyses were used to assess the associations between outcome variables and explanatory variables. The level of significance was set to p < 0.05. The mean number of remaining teeth was 26 (SD: 4). AP was present in 45% of the individuals. Sixteen percent of the individuals had untreated AP and 38% had at least one root-filled tooth with AP. Sixty-six percent of the individuals had one or more root-filled teeth. Untreated AP was significantly associated with a decreasing number of remaining teeth and smoking. All the outcome variables were significantly more prevalent in molars compared with premolars and anterior teeth. Thirty-five percent of the root-filled teeth had AP, and AP was more prevalent in teeth with too short apex-to-filling distance (53%) or unsatisfactory homogeneity (46%). The remaining number of teeth was high, and AP and root-filled teeth were prevalent in the present young-elderly population. A notable amount of untreated AP was observed, especially in smokers. The findings in the present study indicate a substantial need for dental care associated with endodontic conditions in the future elderly.


Dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (F-18 FET) PET for glioma grading: assessment of individual probability of malignancy.
(1) To investigate the diagnostic value of some O-(2-[F]fluoroethyl)-L-tyrosine (F-18 FET) indices derived from the dynamic acquisition to differentiate low-grade gliomas from high-grade; (2) to analyze the course of tumor time-activity curves (TACs); and (3) to calculate the individual probability of a high-grade glioma using the logistic regression. Seventeen low-grade (WHO I-II) and 15 high-grade (WHO III-IV) gliomas were studied with dynamic F-18 FET PET. Regions of interests were drawn over the tumor and contralateral brain, and TACs were analyzed. We considered early standardized uptake value (SUV), middle SUV, late SUV, early-to-middle SUV tumor ratio, early-to-late SUV tumor ratio; time to peak (Tpeak), in minutes, from the beginning of the dynamic acquisition up to the maximum SUV of the tumor; and SoD (sum of the frame-to-frame differences). To assess the individual probability of high-grade, logistic regression was also used. High-grade gliomas showed significantly (P < 0.0001) higher values when compared with low-grade gliomas in early SUV, early-to-middle ratio, early-to-late ratio, Tpeak, and SoD. For the grading of gliomas, the best indices were early-to-middle ratio and Tpeak providing a diagnostic accuracy of 94%. TACs analysis provided an 87% diagnostic accuracy. For individual high-grade diagnosis, the logistic regression provided 93% sensitivity, 100% specificity, and 97% accuracy. Early-to-middle SUV tumor ratio and Tpeak were the best indices for assessing the grading of gliomas. Since early-to-middle ratio derives from the first 35 minutes of the dynamic acquisition, the PET study could last half an hour instead of 1 hour. By logistic regression, it is possible to assess the individual probability of high-grade, useful for prognosis and treatment.


EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic β-cells.
Postnatal expansion of the pancreatic β-cell mass is required to maintain glucose homeostasis immediately after birth. This β-cell expansion is regulated by multiple growth factors, including glucose, insulin, insulin-like growth factor (IGF-1) and epidermal growth factor (EGF). These mitogens signal through several downstream pathways (AKT, ERK, STAT3, and JNK) to regulate the survival and proliferation of β-cells. Survivin, an oncofetal protein with both pro-proliferative and anti-apoptotic properties, is a known transcriptional target of both IGF-1 and EGF in cancer cells. Here, we analyzed the effects of the β-cell mitogens IGF-1 and EGF on survivin regulation in the established pancreatic β-cell model cell lines, MIN6 and INS-1 and in primary mouse islets. In pancreatic β-cells, treatment with glucose, insulin, or EGF increased survivin protein levels at early time points. By contrast, no significant effects on survivin were observed following IGF-1 treatment. EGF-stimulated increases in survivin protein were abrogated in the presence of downstream inhibitors of the Raf-1/MEK/ERK pathway. EGF had no significant effect on survivin transcription however it prolonged the half-life of the survivin protein and stabilized survivin protein levels by inhibiting surviving ubiquitination. This study defines a novel mechanism of survivin regulation by EGF through the Raf-1/MEK/ERK pathway in pancreatic β-cells, via prolongation of survivin protein half-life and inhibition of the ubiquitin-mediated proteasomal degradation pathway. This mechanism may be important for regulating β-cell expansion after birth.


Activation of Calcitonin Gene-Related Peptide and Adrenomedullin Receptors by PEGylated Adrenomedullin.
Adrenomedullin (AM) improves colitis in animal models and patients with inflammatory bowel disease. We have developed a PEGylated AM derivative (PEG-AM) for clinical application because AM has a short half-life in the blood. However, modification by addition of polyethylene glycol (PEG) may compromise the function of the original peptide. In this paper, we examined the time course of cAMP accumulation induced by 5 and 60 kDa PEG-AM and compared the activation of calcitonin gene-related peptide (CGRP), AM1 and AM2 receptors by AM, 5 and 60 kDa PEG-AM. We also evaluated the effects of antagonists on the action of 5 and 60 kDa PEG-AM. PEG-AM stimulated cAMP production induced by these receptors; the increase in cAMP levels resulting from application of PEG-AM peaked at 15 min. Moreover, PEG-AM activity was antagonized by CGRP (8-37) or AM (22-52) (antagonists of CGRP and AM receptors, respectively) and the maximal response was not suppressed. These findings indicate that the effects of PEG-AM are similar to those of native AM.


The Impact of 3D Implant Position on Emergence Profile Design.
Implant position and soft tissue thickness have a direct influence on implant abutment design. The goal is to place the implant in the optimal spatial position to maintain the adjacent bone and soft tissues. When the implant is not placed ideally, prosthetic variations to abutments and restorations must be made, which may limit the esthetic appearance of the final restoration or alter the biologic environment of the bone and tissues. This article illustrates and explains the effect of different implant positions on the emergence profile design in order to assist the clinician with treatment planning and selection in various clinical situations.


Simultaneous medullary carcinoma, papillary carcinoma and granulomatous inflammation of the thyroid.
Thyroid tumours with both papillary and medullary carcinoma features are rare and represent less than 1% of all thyroid malignancies. These tumours have a different clinical presentation and biological behaviour from tumours that have only papillary or medullary carcinoma features. The phenomenon of mixed thyroid tumours can be observed in two settings--a mixed tumour showing dual differentiation, or a collision tumour. For a precise diagnosis of this rare mixed thyroid carcinoma, fine needle aspiration cytology results should be correlated with serum calcitonin and thyroglobulin levels. The diagnosis should also be confirmed using immunocytochemistry. Surgery is the treatment of choice, and the role of postoperative radioiodine is controversial. We herein report the case of a 35-year-old man with a mixed medullary-papillary carcinoma of the thyroid, which presented with C-cell hyperplasia, granulomatous inflammation and metastasis to the cervical lymph nodes. The patient was treated with total thyroidectomy and nodal clearance. This case highlights the need for awareness of coexistent entities as they warrant separate treatments.


Adnexal torsion: the contribution of color Doppler sonography to diagnosis and post-operative follow-up.
Ovarian torsion is often difficult to diagnose due to non-specific clinical and clinical and ultrasonographic findings. We demonstrated the use of color Doppler for the early diagnosis of ovarian torsion and for post-operative follow-up until the normalization of the preserved ovary was confirmed by subsequent viable pregnancy. Color Doppler flow assessment can be useful as both a diagnostic tool and for evaluating the recovery of the affected ovary after conservative surgical treatment.


An 'endless struggle': a qualitative study of general practitioners' and practice nurses' experiences of managing multimorbidity in socio-economically deprived areas of Scotland.
To understand general practitioners' (GPs) and practice nurses' (PNs) experiences of managing multimorbidity in deprived areas and elicit views on what might help. Qualitative interviews with 19 GPs and PNs in four practices with a high percentage of patients living in the top 15% most deprived areas of Scotland. Data were analysed using constant comparison. Professionals' discussions of how they managed multimorbidity captured: (1) definitions of multimorbidity that included multiple social, psychological, and health problems associated with deprivation; (2) descriptions of the 'endless struggle' of patients trying to manage illnesses in the midst of chaotic lives with limited personal, social, and material resources; (3) accounts of the ongoing struggle of professionals trying to manage, with personal consequences for some; and (4) ideas on what might help, including 'whole person' approaches. Professionals' discussions of the difficulties that they face personally and attempt to help those most in need reflect both the continuing existence of the 'inverse care law' and the need for whole system changes to enhance the effectiveness of primary care for patients with multimorbidity in deprived areas.


Asthma control test reflects not only lung function but also airway inflammation in children with stable asthma.
Objective: Various numerical asthma control tools have been developed to distinguish different levels of symptom control. We aimed to examine whether the asthma control test (ACT) is reflective of objective findings such as lung function, fractional exhaled nitric oxide (FeNO) and laboratory data in patients with stable asthma.Methods: We included patients who were enrolled in the Korean Childhood Asthma Study. ACT, spirometry, blood tests and FeNO were performed in patients after stabilization of their asthma. We examined differences among spirometry parameters, blood tests and FeNO according to control status as determined by ACT and investigated for any significant correlations.Results: The study population consisted of 441 subjects. Spirometry showed that forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity and FEV1/forced vital capacity were all significantly higher in the controlled asthma group. Likewise, FeNO and percent-change in FEV1 were both significantly lower in the controlled asthma group. In blood tests, the eosinophil fraction was significantly lower in the controlled asthma group while white blood cell count was significantly higher in the controlled asthma group. Lastly, among the various factors analyzed, only provocative concentration of methacholine causing a 20% fall in FEV1 significantly correlated with ACT score.Conclusion: ACT is useful as part of the routine evaluation of asthmatic children and should be used as a complement to existing tools such as spirometry and FeNO measurement.


Janus kinase/signal transducer and activator of transcription 3 signaling pathway is crucial in chemokine production from hepatocytes infected by dengue virus.
Hepatocytes are one of the important targets in dengue virus (DV) infection. Chemokines produced in DV infection play important immunopathogenic roles. We previously showed that DV infection can directly activate signal transducer and activator of transcription 3 (STAT3) in dendritic cells. In the present study, we examined the possible involvement of the Janus kinase (JAK)/STAT3 pathway in chemokine production from DV-infected hepatocytes. HepG2 cells were infected by DV. The activation of STAT3, nuclear factor-kappaB (NF-κB) and other transcription factors was determined by Western blotting or electrophoretic mobility shift assay. The concentrations of chemokines were measured by enzyme-linked immunosorbent assay. Virus titers were determined by plaque assays. A genetic manipulation with short hairpin RNA (shRNA) was applied to knock-down STAT3. Chemotaxis assays were used to evaluate cell migration. We observed that DV infection induced phosphorylation of STAT3 and its DNA-binding activity and such effects were attenuated by the inhibitor of JAK2 or JAK3. Blocking JAK2 or JAK3 reduced DV-induced cell migration and production of chemokines like interleukin-8 and regulated upon activation, normal T-cell expressed and secreted (RANTES). At high doses, the JAK2 but not JAK3 inhibitor could significantly inhibit DV production. Knocking down STAT3 with shRNA suppressed DV-induced STAT3, NF-κB and AP-1 activation. Furthermore, reduction of STAT3 suppressed DV-induced chemokine production and cell migration but had no effect on virus production. In conclusion, the results show that the JAK/STAT3 pathway is critical in chemokine production from DV-infected hepatocytes. Targeting this pathway may be of benefit in the therapy of DV-induced immunopathologies.


Lethal Clostridium difficile Colitis Associated with Paclitaxel and Carboplatin Chemotherapy in Ovarian Carcinoma: Case Report and Review of the Literature.
Clostridium difficile colitis, although rare, could represent a serious complication following chemotherapy. Prior antibiotic use has been considered the single most important risk factor in the development of C. difficile infection. Recently, the association between antineoplastic therapy and C. difficile-associated diarrhea in the absence of a prior antibiotic therapy has become more apparent. A 75-year-old woman with serous adenocarcinoma of the ovary developed lethal pancolitis caused by C. difficile after five cycles of paclitaxel- and carboplatin-based chemotherapy. She presented with diarrhea, coffee-ground emesis, and oliguria and was hospitalized immediately for aggressive treatment. Despite all the medical efforts, her condition worsened and she died after twenty days. We describe the second case reported of a patient developing a severe C. difficile colitis following chemotherapy without any recent antibiotic use and review the data of the literature, emphasizing the need to a prompt diagnosis and management that can significantly decrease the morbidity and life-threatening complications associated with this infection.


Prevalence of epilepsy in children (a population survey report).
A population based epidemiologic study carried out in a lower socioeconomic suburb of Karachi, identified 23 children with epilepsy among 994 children (3-9 year old) surveyed for childhood disabilities. Nineteen had major epilepsy, 2 petitmal and one each had focal motor and myoclonic attacks. The high frequency of epilepsy may be due to consanguinity, central nervous system, infections and birth and accidental trauma.


Recent Advances in RAFT Polymerization: Novel Initiation Mechanisms and Optoelectronic Applications.
Reversible addition-fragmentation chain transfer (RAFT) is considered to be one of most famous reversible deactivation radical polymerization protocols. Benefiting from its living or controlled polymerization process, complex polymeric architectures with controlled molecular weight, low dispersity, as well as various functionality have been constructed, which could be applied in wide fields, including materials, biology, and electrology. Under the continuous research improvement, main achievements have focused on the development of new RAFT techniques, containing fancy initiation methods (e.g., photo, metal, enzyme, redox and acid), sulfur-free RAFT system and their applications in many fields. This review summarizes the current advances in major bright spot of novel RAFT techniques as well as their potential applications in the optoelectronic field, especially in the past a few years.


Parents' Maltreatment Histories, Dimensions of Emotion Regulation, and Connections to Offspring Self-Regulation: A Sex-Specific Transmission Pathway.
Parents with childhood maltreatment histories are at risk for emotion regulation (ER) problems, which are associated with reduced self-regulation among their offspring. However, gaps remain in the literature regarding this indirect transmission pathway. First, ER consists of multiple dimensions and it is unclear which dimension is most affected by childhood maltreatment. Second, less is known regarding which parental ER dimension is linked to offspring self-regulation. Thus, the present study aimed to examine the direct and indirect associations between parental maltreatment histories and child self-regulatory capacity via dimensions of parental ER. In this cross-sectional study, 101 youth (75% African American/Black; 53% female; M age = 10.28; SD = 1.19) and their primary caregivers were recruited from a low-income community in the Southeastern United States. Structural equation modeling was used to model the effect of parents' self-reported childhood maltreatment on youth physiological self-regulation (measured by heart rate variability reactivity [HRV-R]), via parents' self-reported ER. Parental maltreatment history was significantly associated with five of the six components of ER. Further, the indirect effect of parents' childhood maltreatment on child HRV-R was significant when parents reported more difficulty engaging goal-directed behaviors. Moderation analyses by sex showed that daughters had greater dysregulation regardless of parental maltreatment histories, while parents' ER was found to play a more significant role in the intergenerational transmission of dysregulation to sons. The current study extends the literature on self-regulation development in children of low-income, maltreatment-exposed parents. Our study may inform parent-child interventions for improving self-regulation.


Dilute Alloys Based on Au, Ag, or Cu for Efficient Catalysis: From Synthesis to Active Sites.
The development of new catalyst materials for energy-efficient chemical synthesis is critical as over 80% of industrial processes rely on catalysts, with many of the most energy-intensive processes specifically using heterogeneous catalysis. Catalytic performance is a complex interplay of phenomena involving temperature, pressure, gas composition, surface composition, and structure over multiple length and time scales. In response to this complexity, the integrated approach to heterogeneous dilute alloy catalysis reviewed here brings together materials synthesis, mechanistic surface chemistry, reaction kinetics, in situ and operando characterization, and theoretical calculations in a coordinated effort to develop design principles to predict and improve catalytic selectivity. Dilute alloy catalysts─in which isolated atoms or small ensembles of the minority metal on the host metal lead to enhanced reactivity while retaining selectivity─are particularly promising as selective catalysts. Several dilute alloy materials using Au, Ag, and Cu as the majority host element, including more recently introduced support-free nanoporous metals and oxide-supported nanoparticle "raspberry colloid templated (RCT)" materials, are reviewed for selective oxidation and hydrogenation reactions. Progress in understanding how such dilute alloy catalysts can be used to enhance selectivity of key synthetic reactions is reviewed, including quantitative scaling from model studies to catalytic conditions. The dynamic evolution of catalyst structure and composition studied in surface science and catalytic conditions and their relationship to catalytic function are also discussed, followed by advanced characterization and theoretical modeling that have been developed to determine the distribution of minority metal atoms at or near the surface. The integrated approach demonstrates the success of bridging the divide between fundamental knowledge and design of catalytic processes in complex catalytic systems, which can accelerate the development of new and efficient catalytic processes.


Novel agents to inhibit microbial virulence and pathogenicity.
The rising levels of antibiotic resistance in pathogenic microorganisms create an urgent need for new antimicrobial agents that are not affected by resistance mechanisms already present in the bacterial population. Targeting virulence is one of the alternative approaches to find new molecules to treat infections due to resistant bacteria. Novel strategies to identify these new antimicrobial agents have been reported. A variety of virulence factors are now the target for inhibition mainly in the antibacterial field. This review focuses exclusively on the new virulence inhibitors published in patents (worldwide collection of patents filed) or in the literature since 2006. New efficacy in vitro assays have been developed allowing screening of large numbers of molecules. These inhibitors are mainly antibacterial molecules, a few natural products, peptides and antibodies. A growing number of these published studies provide results showing a proof of concept with antivirulence compounds that were able to prevent or treat an infection in vivo. Moreover, some new antivirulence agents could inhibit virulence mechanisms that are common to different related pathogenic species, extending the potential spectrum of antivirulence compounds. The progress reported recently for antivirulence molecules at the preclinical stages should allow new classes of molecules to enter into development as new antimicrobial agents with new mechanisms of action.


Selection bias in health maintenance organizations: analysis of recent evidence.
An analysis of recent research regarding selection bias in health maintenance organizations (HMO's) is presented in this article. Review of the available literature leads one to conclude that prepaid group practice HMO's do experience favorable selection. It has been demonstrated in numerous studies that prior use of health services by HMO enrollees is less than prior use of health services by those who remain in the fee-for-service sector, and there is considerable evidence that shows a statistically significant positive relationship between prior use and current use. This is true for both those under 65 years of age and those 65 years of age or over.


Improving Communication Between the Emergency Department and Radiology Department With a Novel Web-Based Tool in an Urban Academic Center.
Streamlining communication between radiology and referring services is vital to ensure appropriate care with minimal delays. Increased subspecialization has led to compartmentalization of the radiology department with many physicians working in disparate areas. At our hospital, we anecdotally noted that a significant portion of incoming phone calls were misdirected to the wrong workstations. This resulted in wasted time, unnecessary interruptions, and delays in care because the referring clinicians could not efficiently navigate the radiology department staffing structure. Our quality improvement project involved developing a web-based tool allowing the emergency department (ED) to more efficiently contact the appropriate radiology desk and reduce misdirected phone calls. Surveys were sent to radiology residents and ED providers (attendings, residents, physician assistants) to assess how often phone calls were misdirected to the wrong radiology station. Radiology residents were asked which stations received the most misdirected phone calls, and what station the caller was often looking for. ED providers were asked which stations they intended when they were told they called the wrong station, and a series of questions in the survey assessed their knowledge of commonly called radiology station (Plain Film, CT Body, Ultrasound, Neuoradiology, Pediatrics, and Overnight Desk). ED and radiology physicians worked together to design a simple, easily accessed web-based tool that allowed the ED clinicians to determine which station should be called during for each hour of the day, which integrated differences in staffing by radiology throughout the day. After the tool had been implemented for 8 months, surveys were again sent to radiology residents and ED clinicians asking the same questions as before to assess for any significant change in response. Additional questions were added to the ED survey to assess awareness of the new tool. An interactive, easily updated schedule with optimal contact numbers was made available through the ED intranet. The design allowed for easy modification of contact numbers over time to accommodate changes in coverage location or staffing models. Prior to implementation contact information was presented on a static screen, which was unable to be changed and included multiple incorrect and defunct numbers. Additionally, contact defaulted to a general radiology pager, which was carried by a resident only responsible for plain films for most of the day. Numbers included in the new intranet tool were all pertinent reading room stations, all scheduling desks, and all technologist workspaces. Different schedules were provided for weekdays and weekends. Initial survey results showed that prior to the intervention, 74% of radiology residents said they received misdirected phone calls at least twice a day, and 57.9% of ED respondents reached the wrong recipient at least once per day. Frequencies of misdirected calls dropped to 58.4% of radiology residents (P = 0.37) and 17.9% of ED respondents (P < 0.01) on follow-up surveys 8 months after the tool was established. After establishing the new tool, 82.1% of ED respondents were aware of the new intranet contact tool and were using it to contact radiology. On the series of questions assessing ED respondents' knowledge of radiology numbers, over 50% of respondents knew the correct answer or answered using the call sheet after implementation; this resulted in statistically significant increases in accuracy for Body, Neuroradiology, and Pediatric radiology stations. Furthermore, with the exception of ED plain films, there was a statistically significant reduction in number of responses who said the general radiology pager should be called for reads. Fifty percent of radiology residents believed there was a reduction in the number of misdirected phone calls from the ED with this tool. Our tool was successful in accomplishing multiple goals. First, over 80% of ED respondents adopted the new tool. Second, the number of misdirected phone calls based on the subjective perception of ED respondents and radiology residents was reduced. Third, we objectively improved the ED respondents' behavior pattern in contacting the radiology department by either calling the correct number using the call tool, and by reducing the number of respondents who use the pager. Going forward, we hope to be able to expand use of this tool throughout the hospital in order to provide more timely and efficient care with other services by streamlining access between referring services and the appropriate radiology recipients.


Evidence for negative feature guidance in visual search is explained by spatial recoding.
Theories of attention and visual search explain how attention is guided toward objects with known target features. But can attention be directed away from objects with a feature known to be associated only with distractors? Most studies have found that the demand to maintain the to-be-avoided feature in visual working memory biases attention toward matching objects rather than away from them. In contrast, Arita, Carlisle, and Woodman (2012) claimed that attention can be configured to selectively avoid objects that match a cued distractor color, and they reported evidence that this type of negative cue generates search benefits. However, the colors of the search array items in Arita et al. (2012) were segregated by hemifield (e.g., blue items on the left, red on the right), which allowed for a strategy of translating the feature-cue information into a simple spatial template (e.g., avoid right, or attend left). In the present study, we replicated the negative cue benefit using the Arita et al. (2012), method (albeit within a subset of participants who reliably used the color cues to guide attention). Then, we eliminated the benefit by using search arrays that could not be grouped by hemifield. Our results suggest that feature-guided avoidance is implemented only indirectly, in this case by translating feature-cue information into a spatial template.


Lower limb strength in professional soccer players: profile, asymmetry, and training age.
Kicking and cutting skills in soccer are clearly unilateral, require asymmetrical motor patterns and lead to the development of asymmetrical adaptations in the musculoskeletal function of the lower limbs. Assuming that these adaptations constitute a chronicity-dependent process, this study examined the effects of professional training age (PTA) on the composite strength profile of the knee and ankle joint in soccer players. One hundred soccer players (n=100) with short (5-7 years), intermediate (8-10 years) and long (>11 years) PTA were tested bilaterally for isokinetic concentric and eccentric strength of the knee and ankle muscles. Knee flexion-extension was tested concentrically at 60°, 180° and 300 °/sec and eccentrically at 60° and 180 °/sec. Ankle dorsal and plantar flexions were tested at 60 °/sec for both the concentric and eccentric mode of action. Bilaterally averaged muscle strength [(R+L)/2] increased significantly from short training age to intermediate and stabilized afterwards. These strength adaptations were mainly observed at the concentric function of knee extensors at 60°/sec (p = 0. 023), knee flexors at 60°/sec (p = 0.042) and 180°/sec (p = 0.036), and ankle plantar flexors at 60o/sec (p = 0.044). A linear trend of increase in isokinetic strength with PTA level was observed for the eccentric strength of knee flexors at 60°/sec (p = 0.02) and 180°/sec (p = 0.03). Directional (R/L) asymmetries decreased with PTA, with this being mainly expressed in the concentric function of knee flexors at 180°/sec (p = 0.04) and at 300 °/sec (p = 0.03). These findings confirm the hypothesis of asymmetry in the strength adaptations that take place at the knee and ankle joint of soccer players mainly along with short and intermediate PTA. Players with a longer PTA seem to adopt a more balanced use of their lower extremities to cope with previously developed musculoskeletal asymmetries and possibly reduce injury risk. This has certain implications regarding proper training and injury prevention in relation to professional experience in soccer. Key pointsMuscle strength increased from the low (5-7 years) to the intermediate professional training age (8-10 years) and stabilized thereafter.Soccer practicing and competition at the professional level induces critical strength adaptations (asymmetries) regarding the function of the knee and ankle musculature.Soccer players with long professional training age showed a tendency for lower isokinetic strength asymmetries than players with intermediate and short professional training age.


[Design space approach to optimize first ethanol precipitation process of Dangshen].
Design space approach is applied in this study to enhance the robustness of first ethanol precipitation process of Codonopsis Radix (Dangshen) by optimizing parameters. Total flavonoid recovery, dry matter removal, and pigment removal were defined as the process critical quality attributes (CQAs). Plackett-Burman designed experiments were carried out to find the critical process parameters (CPPs). Dry matter content of concentrated extract (DMCE), mass ratio of ethanol to concentrated extract (E/C ratio) and concentration of ethanol (CEA) were identified as the CPPs. Box-Behnken designed experiments were performed to establish the quantitative models between CPPs and CQAs. Probability based design space was obtained and verified using Monte-Carlo simulation method. According to the verification results, the robustness of first ethanol precipitation process of Dangshen can be guaranteed by operating within the design space parameters. Recommended normal operation space are as follows: dry matter content of concentrated extract of 45.0% - 48.0%, E/C ratio of 2.48-2.80 g x g(-1), and the concentration of ethanol of 92.0% - 92.7%.


Decoupling eye and hand movement control: visual short-term memory influences reach planning more than saccade planning.
When reaching for objects, humans make saccades to fixate the object at or near the time the hand begins to move. In order to address whether the CNS relies on a common representation of target positions to plan both saccades and hand movements, we quantified the contributions of visual short-term memory (VSTM) to hand and eye movements executed during the same coordinated actions. Subjects performed a sequential movement task in which they picked up one of two objects on the right side of a virtual display (the "weapon"), moved it to the left side of the display (to a "reloading station") and then moved it back to the right side to hit the other object (the target). On some trials, the target was perturbed by 1° of visual angle while subjects moved the weapon to the reloading station. Although subjects did not notice the change, the original position of the target, encoded in VSTM, influenced the motor plans for both the hand and the eye back to the target. Memory influenced motor plans for distant targets more than for near targets, indicating that sensorimotor planning is sensitive to the reliability of available information; however, memory had a larger influence on hand movements than on eye movements. This suggests that spatial planning for coordinated saccades and hand movements are dissociated at the level of processing at which online visual information is integrated with information in short-term memory.


Starting a home hemodialysis program: single center experiences.
Home hemodialysis (HHD) has been used only in a minority of patients over past years although it may offer significant advantages over the other renal replacement therapies. This study describes the systems for and the initial results of starting a HHD program. A program for HHD was instituted at a university hospital having more than 20 years of experience in training patients for self-care hemodialysis. A working group designed the patient and partner education program, installations, water quality assurance, logistics, and control systems. Between May 1998 and May 2001, 37 patients with a mean age of 48.3 +/- 12.5 (24-71) years were trained for HHD (1.0 patient/month) the mean training time being 2.0 +/- 0.6 (1-3) months. Four patients had no helper at home. The dialysis schedules (timing, frequency, duration) were individualized at home 41% of the patients having more frequent and/or longer treatments (including long-slow night and daily short HHD). The weekly dialysis time increased from 13.9 +/- 1.5 (CI 13.4-14.4) initially to 15.5 +/- 3.7 (CI 14.2-16.7) h (p = 0.008) at the end of follow-up. Significantly (p < 0.05) increased serum creatinine concentration was observed during the follow-up suggesting for an increased muscle mass. Initially 32% and at the end of follow-up 60% of the patients required no antihypertensive drugs (p < 0.05). Seventeen of the 21 drop-outs were caused by renal transplantation and the most common causes necessitating hospital back-up were related to vascular access. In conclusion the HHD program started in a unit having experience on and commitment for training self-care hemodialysis enabled individualization of the dialysis schedules resulting in the institution of long-slow (night) and alternate day as well as daily HHD therapies. It improved the control of hypertension renal transplantation being the single most common cause of drop-out.


Effects of a training program on resting plasma 2-hydroxycatecholestrogen levels in eumenorrheic women.
Catecholestrogens (CE) represent a major metabolic pathway in estrogen metabolism. Previous information on CE and training is limited to two cross-sectional studies that did not involve standardized training. Our purpose, by means of a prospective design, was to evaluate the effects of a brief, exhaustive training program on resting plasma concentrations of 2-hydroxy CE. The experimental design spanned two menstrual cycles; a control cycle and a training cycle. The subjects were nine previously untrained, eumenorrheic women [body fat: 24.8 +/- 1.0 (SE) %]. Data were collected during the follicular (FPh) and the luteal phases (LPh). Posttraining FPh and LPh tests were held the day after the last day of a 5-day period of training on a cycle ergometer. Total 2-hydroxyestrogens (2-OHE) averaged 200 +/- 29 pg/ml during the FPh and 420 +/- 54 pg/ml during the LPh (P < 0.05). Levels of total 2-methoxyestrogens (2-MeOE) were 237 +/- 32 pg/ml during the FPh and 339 +/- 26 pg/ml during the LPh (P < 0.05). After training, although the plasma levels of 2-OHE significantly decreased (21%; P < 0.05) during the LPh, the actual CE formation (as estimated from the 2-OHE-to-total estrogens ratio) increased (+ 29%; P < 0.05). CE activity, as expressed by the 2-MeOE-to-2-OHE ratio, showed significantly higher values in both phases (FPh, + 14%; LPh, + 13%; P < 0.05). At the same time, resting levels of norepinephrine (NE) were increased by 42% (P < 0.05). CE strongly inhibit biological decomposition of NE by catechol-O-methyltransferase (COMT). Results of the present study suggest that, in response to training, CE are increasingly competing with the enzyme COMT, thus preventing premature NE deactivation.


Plasma concentration of coagulation and fibrinolysis factors and platelet function in hypertension.
Fifty-one patients with mild hypertension were evaluated in relation to the plasma concentrations of coagulation and fibrinolysis factors as well as for the aggregability of their platelets. In a considerable number of the patients (18/51), a significantly enhanced in vitro ADP (2 mumol/l)-induced aggregation was found. In the coagulation line significant increases could be demonstrated in fibrinogen, fibrin monomers and thrombin-antithrombin III. The fibrinolysis system showed significant increases for D-dimers, tissue plasminogen activator antigen and plasminogen activator inhibitor, whereas the tissue plasminogen activator activity was significantly diminished. Remarkably, there seems to be a discrepancy between the (low) tissue plasminogen activator activity and the (higher) plasminogen activator antigen concentration. Alterations in the plasma concentrations of the investigated coagulation and fibrinolysis factors and in the aggregability of the platelets are indicative of an involvement of coagulation, fibrinolysis and platelets in hypertension, which can be considered as partial risk factors for thrombophilia.


Amino acid homologies between human biotinidase and bacterial aliphatic amidases: putative identification of the active site of biotinidase.
A search of protein databases revealed amino acid homologies among human biotinidase, bacterial aliphatic amidases, and bacterial and plant nitrilases. Amino acids YRK(210-212) of biotinidase are conserved among the enzyme families. This homology and naturally occurring mutations that cause biotinidase deficiency suggest that this region is essential for enzyme activity and is conserved from bacteria. Cys(245) is likely the cysteine in the active site of biotinidase.


Angpt2/Tie2 autostimulatory loop controls tumorigenesis.
Invasive nonfunctioning (NF) pituitary neuroendocrine tumors (PitNETs) are non-resectable neoplasms associated with frequent relapses and significant comorbidities. As the current therapies of NF-PitNETs often fail, new therapeutic targets are needed. The observation that circulating angiopoietin-2 (ANGPT2) is elevated in patients with NF-PitNET and correlates with tumor aggressiveness prompted us to investigate the ANGPT2/TIE2 axis in NF-PitNETs in the GH3 PitNET cell line, primary human NF-PitNET cells, xenografts in zebrafish and mice, and in MENX rats, the only autochthonous NF-PitNET model. We show that PitNET cells express a functional TIE2 receptor and secrete bioactive ANGPT2, which promotes, besides angiogenesis, tumor cell growth in an autocrine and paracrine fashion. ANGPT2 stimulation of TIE2 in tumor cells activates downstream cell proliferation signals, as previously demonstrated in endothelial cells (ECs). Tie2 gene deletion blunts PitNETs growth in xenograft models, and pharmacological inhibition of Angpt2/Tie2 signaling antagonizes PitNETs in primary cell cultures, tumor xenografts in mice, and in MENX rats. Thus, the ANGPT2/TIE2 axis provides an exploitable therapeutic target in NF-PitNETs and possibly in other tumors expressing ANGPT2/TIE2. The ability of tumor cells to coopt angiogenic signals classically viewed as EC-specific expands our view on the microenvironmental cues that are essential for tumor progression.


Identification of a unique tumor cell subset employing myeloid transcriptional circuits to create an immunomodulatory microenvironment in glioblastoma.
Glioblastoma (GBM) is an aggressive primary brain tumor with unique immunity predominated by myeloid cells. GBM cells have been implicated to evade immune attack through hijacking myeloid-affiliated transcriptional programs to establish an immunosuppressive microenvironment. However, molecular features of immune-evading GBM cells in heterogeneous GBMs and their interactions with immune cells remain unclear. Herein, we employed single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to develop an in silico method for delineating GBM immune signature and identifying new molecular subsets for immunotherapy. We identified a new GBM cell subset, termed TC-6, that harbored immune-invading signature and actively interacted with tumor-associated macrophages (TAMs) to orchestrate an immune-suppressive niche. Proinflammatory transcriptional factors STAT1, STAT2, IRF1, IRF2, IRF3, and IRF7 were identified as the core regulons defining TC-6 subsets. Further immune transcriptome analyses revealed three immune subtypes (C1, C2, and C3). C3 subtype GBMs were enriched with TC-6 cells and immunosuppressive TAMs, and exhibited an immunomodulatory signature that associated with reduced efficacy of anti-PD-1 treatment. Interferon-related DNA damage resistance signaling was upregulated in C3 GBMs, predicting shortened survival of GBM patients who received chemo-radiation treatment. Treatment of OSI-930 as a molecular agent targeting c-kit and VEGFR2 tyrosine kinases may compromise the immunomodulatory signature of C3 GBMs and synergize with chemo-radiation therapy. We further developed a simplified 11-gene set for defining C3 GBMs. Our work identified TC-6 subset as an immune-evading hub that creates an immunomodulatory signature of C3 GBMs, gaining insights into the heterogeneity of GBM immune microenvironment and holding promise for optimized anti-GBM immunotherapy.


Regulation of end-binding protein EB1 in the control of microtubule dynamics.
The regulation of microtubule dynamics is critical to ensure essential cell functions, such as proper segregation of chromosomes during mitosis or cell polarity and migration. End-binding protein 1 (EB1) is a plus-end-tracking protein (+TIP) that accumulates at growing microtubule ends and plays a pivotal role in the regulation of microtubule dynamics. EB1 autonomously binds an extended tubulin-GTP/GDP-Pi structure at growing microtubule ends and acts as a molecular scaffold that recruits a large number of regulatory +TIPs through interaction with CAP-Gly or SxIP motifs. While extensive studies have focused on the structure of EB1-interacting site at microtubule ends and its role as a molecular platform, the mechanisms involved in the negative regulation of EB1 have only started to emerge and remain poorly understood. In this review, we summarize recent studies showing that EB1 association with MT ends is regulated by post-translational modifications and affected by microtubule-targeting agents. We also present recent findings that structural MAPs, that have no tip-tracking activity, physically interact with EB1 to prevent its accumulation at microtubule plus ends. These observations point out a novel concept of "endogenous EB1 antagonists" and emphasize the importance of finely regulating EB1 function at growing microtubule ends.


TRIM proteins and the innate immune response to viruses.
Many TRIM proteins are up-regulated by interferons, suggesting that they might be involved in the innate immune response against viruses. Indeed, some members of the family have been shown to be either regulators of the interferon pathways or to be directly involved in the restriction of viruses. While the mechanisms of actions are varied, the modular organization of these proteins seems to be important for their activities, many of which are linked to the ubiquitination/proteasomal degradation system. The different domains enable the TRIM proteins to interact with either viral components or signaling molecules in the interferon induction pathways.


The Outpatient Approach to Dizziness.
The evaluation of the dizzy patient is complicated by many common pitfalls. The patient's description of symptoms and the standard neurologic examination are often nonspecific or unrevealing, and neuroimaging is most often normal. Over the past several years, research has demonstrated that a refocusing of history taking results in more reliable and diagnostically helpful information. This can guide a targeted expansion of the exam, often with an emphasis on eye movements.


National Prociency Testing Result of CYP2D6*10 Genotyping for Adjuvant Tamoxifen Therapy in China.
Tamoxifen has been successfully used for treating breast cancer and preventing cancer recurrence. Cytochrome P450 2D6 (CYP2D6) plays a key role in the process of metabolizing tamoxifen to its active moiety, endoxifen. Patients with variants of the CYP2D6 gene may not receive the full benefit of tamoxifen treatment. The CYP2D6*10 variant (the most common variant in Asians) was analyzed to optimize the prescription of tamoxifen in China. To ensure referring clinicians have accurate information for genotype-guided tamoxifen treatment, the Chinese National Center for Clinical Laboratories (NCCL) organized a national proficiency testing (PT) to evaluate the performance of laboratories providing CYP2D6*10 genotyping. Ten genomic DNA samples with CYP2D6 wild-type or CYP2D6*10 variants were validated by PCR-sequencing and sent to 28 participant laboratories. The genotyping results and pharmacogenomic test reports were submitted and evaluated by NCCL experts. Additional information regarding the number of samples tested, the accreditation/certification status, and detecting technology was also requested. Thirty-one data sets were received, with a corresponding analytical sensitivity of 98.2% (548/558 challenges; 95% confidence interval: 96.7-99.1%) and an analytic specificity of 96.5% (675/682; 95% confidence interval: 97.9-99.5%). Overall, 25/28 participants correctly identified CYP2D6*10 status in 10 samples; however, two laboratories made serious genotyping errors. Most of the essential information was included in the 20 submitted CYP2D6*10 test reports. The majority of Chinese laboratories are reliable for detecting the CYP2D6*10 variant; however, several issues revealed in this study underline the importance of PT schemes in continued external assessment and provision of guidelines.


The contribution of assets to adaptation to extreme temperatures among older adults.
Climate change and extreme temperatures pose increasing challenges to individuals and their health with older adults being one of the most vulnerable groups. The aim of this paper is to better understand the roles that tangible assets (e.g., physical or financial) and intangible assets (e.g., human or social) play in the way older adults adapt to extreme temperatures, the types of adaptive responses they implement, limits and constraints, as well opportunities for better adaptation. Rather than focusing exclusively on extremes of heat, or considering each type of asset in isolation, the important and novel contribution of this paper is to take an integrated and multi-seasonal qualitative and quantitative approach, that conjointly investigates all categories of assets in relation to the adaptations that independently-living older adults make to both extreme heat and extreme cold. The paper examines the contribution of assets to adaptation to extreme temperatures among older adults living independently in their homes. An innovative mixed methods study with an inter-seasonal approach was implemented in Lisbon, Portugal with interviews and surveys during summer for extreme heat and winter for extreme cold. The ability of participants to adapt to extreme temperatures was found to be dependent on asset context and diversity, and the dynamics through which extreme temperatures enhanced or reduced the stock of assets available. As a result, participants engaged in activities of assets replacement, exchange or substitutions. Despite this, many participants recognised many constraints and limits to their ability to adapt and protect their health and well-being ranging from reduced income, high energy costs and lack of social networks. Opportunities for improving older adults' adaptation were found to exist and strategies, action and investment have been identified by older adults which included life-long education, incentives to improve insulation and local activities. The paper suggests that the implementation of the proposed asset-based approach linking assets and adaptation to extreme temperatures, illustrates the key pathway that individuals, their families and carers, governments, policymakers, researchers and practitioners can follow to ensure effective adaptation and promote health and well-being. Supporting older adults' adaptation to extreme temperatures is possible and can be complemented with efforts to reduce older adults' vulnerability and building resilience to extreme temperatures. These findings pose concrete implications for policy and practice, including for example the need for implementation of measures and actions to reduce poverty, reduce energy costs, improve the quality of the housing stock and improve older adults' social networks.


The relationship between spectral characteristics and perceived hypernasality in children.
The purpose of this study was to quantify perceived hypernasality in children. One-third octave spectra of the isolated vowel [i] were obtained from 32 children with cleft palate and 5 children without cleft palate. Four experienced listeners rated the severity of hypernasality of the 37 speech samples using a 6-point equal-appearing interval scale. When the average 1/3-octave spectra from the hypernasal group and the normal resonance group were compared, spectral characteristics of hypernasality were identified as increased amplitudes between F1 and F2 and decreased amplitudes in the region of F2. Based on the findings of the children's speech, 36 speech samples with manipulated spectral characteristics were used to minimize the influences of voice source characteristics on perceived hypernasality. Multiple regression analysis revealed a high correlation (R = 0.84) between the amplitudes of 1/3-octave bands (1 k, 1.6 k, and 2.5 kHz) and the perceptual ratings. Increased amplitudes of bands between F1 and F2 (1 k, 1.6 kHz) and decreased amplitude of the band of F2 (2.5 kHz) was associated with an increasing perceived hypernasality. These results suggest that the amplitudes of the three 1/3-octave bands are appropriate acoustic parameters to quantify hypernasality in the isolated vowel [i].


[Dirt tattooing following an explosion in a chemistry class].
Traumatic tattooing following an explosion can generally be removed by rubbing with a hard-bristle handbrush within 48 h after the accident occurs. This measure failed, however, in the case of a pupil with extensively dispersed granular material in the face. The patient had mixed approximately 5 g of potassium permanganate and red phosphorus together during a chemistry lesson (!), thereby causing an explosion. A conservative treatment of applying compresses moistened with a sodium bicarbonate solution led to healing without scars.


A new species of Paracapillaroides (Nematoda: Capillariidae) parasitizing Nemadactylus bergi (Perciformes: Latridae) from the Argentine Sea.
A new nematode species, Paracapillaroides acanthocotylus sp. n., is described from the marine fish Nemadactylus bergi (Norman) (Latridae, Perciformes) from waters off Mar del Plata, Argentina (38 degrees 08'S, 57 degrees 32'W) (prevalence 81.8%, mean intensity 12.4 +/- 10.3). The new species is readily distinguished from P. agonostomi Moravec, Salgado-Maldonado et Caspeta-Mandujano, 1999, the only known species of the genus, by having in both sexes a longer oesophagus in relation to total body length. Males of the new species have a shorter and more complex spicule and a markedly different morphology of the spicular sheath; the rays supporting the caudal bursa are also shorter and rounded, instead of digitiform. Furthermore, females of the new species have elevated vulval lips and longer eggs. The complex structure of both the spicule and spicular sheath is unique among all capillariids parasitizing cold-blooded vertebrates. This is the first record of a species of Paracapillaroides in the southwestern Atlantic Ocean.


Protective effects of pravastatin on the embryonic cardiovascular system during hypoxic development.
The use of statins in complicated pregnancy is being considered, as they protect endothelial function in the mother and placenta. However, whether statins affect cardiovascular function in the fetus is completely unknown. Here, we have determined the effects of pravastatin and underlying mechanisms on the cardiovascular system of the hypoxic chicken embryo, a model system that permits the direct effects of pravastatin on the developing offspring to be isolated independently of additional effects on the mother and/or placenta. Chicken embryos were incubated under normoxia or hypoxia (14% O2 ) from day 1 ± pravastatin (1 mg/kg/d) from day 13 of incubation (term is 21 days). On day 19 of incubation, hearts and vessels were isolated to determine changes in the cardiovascular structure and function. The data show that pravastatin protected the hypoxic chicken embryo against impaired cardiovascular dysfunction. Mechanisms involved in this protection included reduced oxidative stress, enhanced NO bioavailability, restored antioxidant defenses and normalized protein expression of RhoA in the embryonic heart, and improved NO-dependent vasodilator mechanisms in the peripheral circulation. Therefore, we show that the treatment of the chronically hypoxic chicken embryo with pravastatin from day 13 of incubation, equivalent to ca. 25 weeks of gestation in human pregnancy, has direct beneficial effects on the embryonic cardiovascular system. Therefore, pravastatin may be a candidate for human clinical translation to rescue fetal cardiovascular dysfunction in risky pregnancy.


Cellular Mechanism Underlying rTMS Treatment for the Neural Plasticity of Nervous System in Drosophila Brain.
Repetitive transcranial magnetic stimulation (rTMS) is used as a research tool and clinical treatment for the non-clinical and clinical populations, to modulate brain plasticity. In the case of neurologic and psychiatric disease, there is significant evidence to suggest that rTMS plays an important role in the functional recovery after neurological dysfunction. However, the causal role for rTMS in the recovery of nervous dysfunction remains unclear. The purpose of the present study is to detect the regulation of rTMS on the excitatory neuronal transmission and specify the mode of action of rTMS on the neural plasticity using Drosophila whole brain. Therefore, we identified the effects of rTMS on the neural plasticity of central neural system (CNS) by detecting the electrophysiology properties of projection neurons (PNs) from adult Drosophila brain after rTMS. Using patch clamp recordings, we recorded the mini excitatory postsynaptic current (mEPSC) of PNs after rTMS at varying frequencies (1 Hz and 100 Hz) and intensities (1%, 10%, 50%, and 100%). Then, the chronic electrophysiology recordings, including mEPSC, spontaneous action potential (sAP), and calcium channel currents from PNs after rTMS at low frequency (1 Hz), with low intensity (1%) were detected and the properties of the recordings were analyzed. Finally, the frequency and decay time of mEPSC, the resting potential and frequency of sAP, and the current density and rise time of calcium channel currents were significantly changed by rTMS. Our work reveals that rTMS can be used as a tool to regulate the presynaptic function of neural circuit, by modulating the calcium channel in a frequency-, intensity- and time-dependent manner.


A self-help approach for high-risk drinking: effect of an initial assessment.
A self-help book was offered to persons wanting to quit or cut down on their alcohol use. Study participants (99 men, 56 women) were recruited through advertisements, screened by telephone, and randomly assigned to 1 of 2 conditions. Book by mail or Assessment + Book (30-min telephone motivational interview plus book by mail). At 3-month follow-up, significantly more participants qualified as moderate drinkers in the Assessment + Book condition (65% vs. 43%), by this criterion: < or = 12 drinks/week and < or = 10% heavy drinking days (5 + drinks if male and 4 + drinks if female; 13.6 g of ethanol per drink). At 12 months there was no effect of condition, but significantly more women than men were rated as moderate drinkers (71% vs. 52%). Collateral informants corroborated the participants' reports of drinking.


Transumbilical single-incision laparoscopy surgery splenectomy plus pericaudial devascularization in one case with portal hypertension: the first report.
Single-incision laparoscopy surgery (SILS) has rapidly developed as both a cosmetic advantage of natural orifice translumenal endoscopic surgery and a standard surgical procedure. In this article, the authors report on the new technique of SILS splenectomy plus pericaudial devascularization with conventional laparoscopic instruments. The technique of SILS splenectomy plus pericaudial devascularization in one patient with portal hypertension was introduced. The procedure was feasible with conventional laparoscopic instruments. Operative time was 240 minutes, and blood loss was 350 mL. No intraoperative or postoperative complications, such as secondary hemorrhage or pancreatic leakage, were recorded. The patient was fully recovered, and the single umbilical scar was well healed. SILS splenectomy plus pericaudial devascularization is feasible when performed by experienced laparoscopic surgeons. It may have the same cosmetic advantage as natural orifice translumenal endoscopic surgery and may offer the safety of conventional laparoscopic operation. As far as the authors are aware, this is the first report.


Photodynamic therapy on rat urinary bladder with intravesical instillation of 5-aminolevulinic acid: light diffusion and histological changes.
Photodynamic therapy (PDT) has the potential to treat extensive premalignant lesions and microinvasive tumors in the bladder, but its use has been hampered by the risk of detrusor muscle damage and prolonged skin photosensitivity. We have shown that the rat urothelium can be sensitized by selectively using a 10% solution of 5-aminolevulinic acid (ALA) at pH 5.5 administered intravesically. This paper evaluates the photodynamic effects on sensitized bladders. The bladders ofs Wistar rats were instilled with ALA solutions of different concentrations at pH 5.5 and subsequently treated with laser light at 630 nm. Bladders were harvested 1 to 7 days after PDT for histological assessment. Under optimum conditions (10% intralipid diffusion medium, light dose 50J) uniform urothelial necrosis was seen after 1 to 2 days; it healed in 7 days without damage to the underlying muscle layer although some increase in collagen was seen in the lamina propria. Overtreatment or poor light distribution resulted in muscle necrosis and scarring. Selective urothelial necrosis is possible with PDT using intravesical ALA. There is now sufficient data for pilot clinical trials to start photodynamic therapy for management of superficial bladder cancer or carcinoma in situ.


Threat-Avoidance Tendencies Moderate the Link Between Serotonin Transporter Genetic Variation and Reactive Aggression.
The short (S) allele of the serotonin transporter-linked promoter region (5-HTTLPR) polymorphism has been linked to reactive aggression in men, but this association is less consistent in females. Reactive aggression has been particularly described as a result of fear-driven defense to threat, but how this interaction between defensive behavior and aggression is expressed in S-allele carriers remains unknown. In order to explore this interplay between 5-HTTLPR genotype, defensive behavior and reactive aggression, we combined genotyping with objective measures of action tendencies toward angry faces in an approach-avoidance task (AAT) and reactive aggression in the Taylor aggression paradigm (TAP) in healthy females, N = 95. This study shows that female S-allele carriers in general display increased implicit reactive aggression (administering aversive white noise) toward opponents. Furthermore, we found that threat-avoidance tendencies moderate the association between 5-HTTLPR genotype and aggression displayed on the TAP. Together, these findings indicate a positive correlation between avoidance of angry faces in the AAT and reactive aggression in the TAP exclusively present in S-allele carriers.


MRS of the brain in patients with anorexia or bulimia nervosa.
Twenty patients with anorexia or bulimia nervosa were prospectively investigated by magnetic resonance spectroscopy (MRS) of the brain. Compared to healthy controls, MRS of those with eating disorders revealed metabolic changes, which seem to be a consequence of their nutritional deficiency.


Preschool children's ability to coordinate spatial perspectives through language and pictures.
To determine preschool children's ability to utilize language in spatial problem solving, 64 children (equal numbers of boys and girls, 3- and 4-year-olds) were asked to identify another's view either verbally or by picture selection. The results indicate that verbalization leads to substantially more correct responses and girls were significantly better than boys across both response modes. The results imply that, despite the claims of several theorists, linguistic processes are accessible for problem solving at an early age.


Therapeutic time window for YAG laser-induced reperfusion of thrombotic stroke in hypertensive rats.
We examined the novel YAG laser-induced reperfusion method in the photothrombotic middle cerebral artery (MCA) occlusion model in spontaneously hypertensive rats. In the 1 h ischemia group, infarct volume was significantly reduced to 41.1 +/- 15.6 mm3 compared with 81.6 +/- 18.3 mm3 in the no-reperfusion group. There were no significant differences in infarct volume among 2 h or 3 h ischemia and no-reperfusion groups. Three of six rats in the 3 h ischemia group showed hemorrhagic infarction. Our present results showed that recirculation must be instituted within 2 h of MCA occlusion to get beneficial effects in our model, supporting the concept of a narrow therapeutic time window for intervention in ischemic stroke.


Haemophagocytic syndrome associated with hepatitis-B virus infection responding to etoposide.
Haemophagocytic syndrome (HPS) secondary to viral infections usually has a variable course and can be life-threatening. We report a 53-year-old male patient who presented with fever, hepatosplenomegaly and pancytopenia. He had deranged liver function, abnormal clotting and markedly elevated serum ferritin. Bone marrow biopsy showed prominent haemophagocytosis. The patient was investigated thoroughly and found to have evidence of chronic hepatitis B-virus (HBV) infection by serological tests and liver biopsy. Other conditions associated with HPS such as lymphoma, malignancy and other viral or bacterial infections were not present. The patient did not respond to steroids, intravenous immunoglobulins or cyclosporin but responded to etoposide and became apyrexial. He also became HBV negative on lamivudine. The patient died of infection later on but there was no evidence of recurrence of HPS. To the best of our knowledge this is the first case report of HPS associated with isolated HBV infection.


Insurance coverage and ambulatory medical care of low-income children: United States, 1980.
In the household survey phase of the National Medical Care Utilization and Expenditure Survey of 1980, a survey was conducted of 17,123 persons who constituted a representative sample of the civilian population in the United States not residing in institutions. Through repeated interviews the survey obtained information on the health conditions of these people, the health care services they received in 1980, the costs of these services, and the sources of payment for services. This report, one of a series of reports on the survey findings, provides a profile of low-income children: Their health insurance coverage, health service use, and expenditures for physician visits. Children under 18 years of age in families below 150 percent of the 1980 Federal poverty level are considered low income. However, children who were ineligible to participate in the survey for part of the year are excluded, such as those who were born, who died, or who were institutionalized in 1980. A physician visit is defined as a face-to-face contact with a physician or a nonphysician working under the supervision of a physician. In addition, visits to nurse practitioners and physician assistants who were reported as "independent providers" are included. Otherwise, visits to independent providers (primarily chiropractors and optometrists), mental health visits, visits by physicians to hospital inpatients, and telephone contacts are excluded. Of the 63.9 million children under 18 years of age in the United States in 1980, about one-fourth (16.8 million) lived in low-income families, according to estimates from the National Medical Care Utilization and Expenditure Survey. Nearly one-half (46 percent) of the 16.8 million low-income children were covered by Medicaid for all or part of 1980: 31 percent were covered by Medicaid only for the full year, 3 percent were covered by Medicaid for part of 1980 and uninsured for the remainder of the year, and 12 percent were covered by both Medicaid and private insurance during the year. An additional 30 percent of the low-income children were privately insured for the full year, while 8 percent had private insurance coverage for part of the year and were uninsured otherwise. Sixteen percent of the children in low-income families, or 2.7 million children, were uninsured for all of 1980. When added to the 3 percent with part year Medicaid coverage and the 8 percent with private coverage part of the year, over one-fourth (28 percent) were uninsured for at least part of 1980.(ABSTRACT TRUNCATED AT 400 WORDS)


Effects of diagnostic inclusion criteria on prevalence and population characteristics in database research.
Studies of serious mental illnesses that use administrative databases have employed various criteria to establish diagnoses of interest. Several studies have assessed the validity of diagnostic inclusion criteria against research diagnoses. However, no studies have examined the effect of diagnostic inclusion criteria on prevalence and population characteristics across such groups. Administrative data for 2003-2010 from the Department of Veterans Affairs were used to calculate prevalence rates and assess effects of varying the diagnostic inclusion criteria on population composition for bipolar disorder, schizophrenia, and posttraumatic stress disorder (PTSD). Specifically, for each diagnosis, mutually exclusive subpopulations were compared on the basis of the following inclusion criteria for a given diagnosis: one treatment encounter, two outpatient encounters or one inpatient encounter, and any two encounters. For bipolar disorder and schizophrenia, effects of excluding individuals who had a competing diagnosis of, respectively, schizophrenia or bipolar disorder in the prior 12 months and since 2002 were also determined. In 2010, moving from the broadest definitions of bipolar disorder (N=120,382), schizophrenia (N=91,977), and PTSD (N=554,028) to the most restrictive definitions reduced prevalence rates by, respectively, 28.7%, 34.9%, and 25.7%, with temporal trends for 2003-2010 paralleling results in 2010. Population composition changes with changing diagnostic inclusion criteria were variable, with predominantly small odds ratios. Population composition was relatively robust across common diagnostic inclusion criteria for each condition. Thus choice of criteria can focus on considerations of diagnostic validity and case-finding needs. Three mechanisms for the impact of diagnostic criteria on population composition in administrative data sets are discussed.