Outcome of ultrasonographic hip abnormalities in clinically stable hips.
A retrospective review was performed of 192 newborn hips in 112 patients referred for hip evaluation. The average age at presentation was 12.7 days, with average radiographic follow-up of 15.9 months. Inclusion criteria for our study were a normal physical examination of the hip without evidence of instability and an ultrasound examination that was considered abnormal. Pavlik harness treatment was chosen at the discretion of the treating physician. At final follow-up, dysplasia was defined as greater than two standard deviations above the mean acetabular index (AI) for age. Group I consisted of 43 hips that had Pavlik treatment, and group II consisted of 149 hips that did not receive treatment. There was no difference in these two groups with respect to risk factors for dysplasia or the initial abnormalities seen on ultrasound evaluation, although patients in group I had less coverage of the femoral head during stress maneuvers. No hip in group I and two (1.3%) hips in group II were considered dysplastic (AI > 2 SD) at final radiographic follow-up (p > 0.10). There was no correlation between the severity of the ultrasound abnormality at birth and the subsequent presence of dysplasia (p > 0.10). The two hips considered dysplastic on radiograph were not being actively treated. When the hip examination of a newborn hip younger than 1 month is normal, a screening ultrasound does not appear to predict accurately subsequent hip dysplasia. In this specific setting, an initial screening ultrasound may be too sensitive and does not appear warranted.


Free and total serum PSA values in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer and BPH. Is F/T PSA a potential probe for dormant and manifest cancer?
Free and total PSA serum concentrations were retrospectively measured in 106 subjects: 45 patients with intraepithelial prostatic neoplasia (PIN), 30 subjects with benign prostatic hypertrophy (BPH) and 31 subjects with untreated prostatic carcinoma. The (F/T) x 100 PSA value is recorded in subjects with the elevated total PSA level (> 4 ng/ml). PIN patients were divided into two groups: a low grade PIN (PIN 1) and high grade PIN (PIN II-III) patients. The mean (F/T) x 100 PSA value in low grade PIN patients was 27.9 +/- 16.2 (range 17.1-41.2, median 25.1) and has been numerically similar to the respective value in BPH subjects (29.1 +/- 13.2, 15.8-48.0, 27.7). These parameters differed markedly (P < 0.01) from the mean (F/T) x 100 PSA value in high grade PIN patients (16.9 +/- 9.0, range 9.9-24.9, median 16.5). The later values were in turn comparable (P > > 0.05) with the respective value measured in untreated prostate cancer patients (14.4 +/- 10.8, 6.6-21.4, 12.6). Hence, values derived from the measurement of free and total serum PSA level may distinguish low grade PIN that prevailingly remains latent disease from high grade PIN that is in most cases not only early prostatic carcinoma but that is often a precursor of an aggressive neoplasm. The published literature is incoherent regarding the influence of tumor spread on F/T PSA level. The cutoff point that divides BPH from cancer may depend on tumor stage. We have not investigated F/T PSA values related to different stages and grades of prostate cancer. The cutoff point of (F/T) x 100 PSA in our study that divides malignant from benign prostate, or latent from manifest cancer, was tentatively assigned as 18 with a specificity of 91% and selectivity of 69%. Our data are based on the application of the CIS assay that, according to the literature, gives higher F-PSA % compared to other respective kits.


The specificity of Burkholderia symbionts in the social amoeba farming symbiosis: Prevalence, species, genetic and phenotypic diversity.
The establishment of symbioses between eukaryotic hosts and bacterial symbionts in nature is a dynamic process. The formation of such relationships depends on the life history of both partners. Bacterial symbionts of amoebae may have unique evolutionary trajectories to the symbiont lifestyle, because bacteria are typically ingested as prey. To persist after ingestion, bacteria must first survive phagocytosis. In the social amoeba Dictyostelium discoideum, certain strains of Burkholderia bacteria are able to resist amoebal digestion and maintain a persistent relationship that includes carriage throughout the amoeba's social cycle that culminates in spore formation. Some Burkholderia strains allow their host to carry other bacteria, as food. This carried food is released in new environments in a trait called farming. To better understand the diversity and prevalence of Burkholderia symbionts and the traits they impart to their amoebae hosts, we first screened 700 natural isolates of D. discoideum and found 25% infected with Burkholderia. We next used a multilocus phylogenetic analysis and identified two independent transitions by Burkholderia to the symbiotic lifestyle. Finally, we tested the ability of 38 strains of Burkholderia from D. discoideum, as well as strains isolated from other sources, for traits relevant to symbiosis in D. discoideum. Only D. discoideum native isolates belonging to the Burkholderia agricolaris, B. hayleyella, and B. bonniea species were able to form persistent symbiotic associations with D. discoideum. The Burkholderia-Dictyostelium relationship provides a promising arena for further studies of the pathway to symbiosis in a unique system.


Symptom control in patients with recurrent ovarian cancer: measuring the benefit of palliative chemotherapy in women with platinum refractory/resistant ovarian cancer.
Most women with advanced ovarian cancer will relapse and subsequently develop platinum-resistant/refractory ovarian cancer. The benefit of treatment is currently based on objective response rates, which are a crude measure of benefit. It would be clinically meaningful if we were better able to measure the benefit of palliative therapy and, in particular, ascertain whether cancer-related symptoms improve with treatment and how this impacts on quality of life. This paper reviews the management of patients with platinum-resistant/refractory ovarian cancer and highlights the gaps in our knowledge and shortcomings with the current approaches to measure the benefit of treatment. The ultimate objective is to describe and encourage recruitment to the Gynecologic Cancer Intergroup study that has recently opened. This study will recruit a large number of patients from around the world in an effort to develop more robust instruments to measure the benefit of chemotherapy and to understand the impact of chemotherapy on symptom control and quality of life. In addition, this study will give us an insight into how all patients are managed rather than a select minority who are treated in clinical trials.


Estrogen receptor-beta is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast.
An estrogen dependency has been suggested for the growth of fibroadenomas: however, thus far, none of the steroid hormone receptors acting on breast tissues has been demonstrated in the stroma of breast fibroepithelial lesions. In this study, the expression of estrogen receptor (ER)-alpha and -beta was investigated by immunohistochemistry in 33 fibroadenomas and in 30 benign, three borderline and seven malignant phyllodes tumors, all with spindle cell growth and in one distant metastasis. In addition, the presence of ER-beta mRNA and its variants was evaluated by RT-PCR in microdissected stroma. The possible correlation between hormone receptor expression and differentiation processes of stromal cells was investigated by smooth muscle actin and calponin immunostaining. ER-beta was the only hormone receptor expressed by stroma of fibroadenomas and phyllodes tumors, both at protein and mRNA level. The highest percentage of ER-beta was observed in fibroadenomas with cellular stroma and in phyllodes tumors. In both lesions, ER-beta-positive stromal cells showed expression of smooth muscle actin and/or calponin, as demonstrated by double immunostaining. In addition, the mean age at diagnosis was significantly lower in patients with ER-beta-positive vs ER-beta-negative fibroadenomas. In contrast, in phyllodes tumors, ER-beta expression was higher in older patients. In conclusion, (i) only ER-beta is detected in the stroma of fibroadenomas and phyllodes tumors; (ii) its expression correlates with the expression of smooth muscle markers and suggests a role of ER-beta in myofibroblastic differentiation of stromal cells. These two results, together with the young age of patients carrying fibroadenomas with highly ER-beta-positive stroma cells, may further indicate a hormone-receptor mechanism involved in regulating the growth of fibroadenomas. Conversely, the older age of patients with ER-beta-rich phyllodes tumors suggests that mechanisms, probably independent from estrogen stimulation, act on the growth of these tumors.


Use of freshwater plants for phytotoxicity testing: a review.
Phytotoxicity data for aquatic plants have served a relatively minor role in regulatory decisions concerning the environmental hazard of most potential contaminants. A variety of phytotoxicity tests have been conducted with freshwater green algae, duckweed, blue-green algae, diatoms and rooted macrophytes (whole plants and seeds). Several test methods have been standardized for microalgae which are used primarily with chemicals, effluents, contaminated sediment elutriates and hazardous waste leachates. Current scientific understanding concerning the phytotoxic effects of these contaminants is based mostly on results for a few green algae. The greatest limitation of these results is their uncertain environmental relevance due to the large interspecific variation in response of standard algal test species and the unrealistic experimental test conditions. Results of the few field validation toxicity tests conducted to resolve this uncertainty have been chemical-specific and unpredictable. Aquatic vascular plants have been used less frequently than algae as test species. Duckweeds have been used more often than rooted submersed species but the uncertain nature of their sensitivities relative to animal and other plant species has limited their use. Regulatory interest in wetland protection, contaminated sediment evaluations and sediment quality criteria development will result in increased use of whole rooted plants and their seeds as test species. Overall, regardless of the test species, if phytotoxicity data are to be more available and effective in the hazard assessment process, additional information concerning species sensitivity, and environmental relevance of the results will be needed.


Protease-activated ratiometric fluorescent probe for pH mapping of malignant tumors.
A protease-activated ratiometric fluorescent probe based on fluorescence resonance energy transfer between a pH-sensitive fluorescent dye and biocompatible Fe3O4 nanocrystals was constructed. A peptide substrate of MMP-9 served as a linker between the particle quencher and the chromophore that was covalently attached to the antitumor antibody. The optical response of the probe to activated MMP-9 and gastric cell line SGC7901 tumor cells was investigated, followed by in vivo tumor imaging. Based on the ratiometric pH response to the tumor microenvironment, the resulting probe was successfully used to image the pH of subcutaneous tumor xenografts.


Sonographic features of gastrointestinal lymphoma in 15 dogs.
The purpose of this study is to describe the sonographic appearance of lymphoma of the gastrointestinal tract in dogs. A retrospective review was conducted and patients with gastrointestinal lymphoma diagnosed by histopathology (including immunohistochemistry, where available) or cytology that had an abdominal ultrasound were included. Four of 15 (26·7%) cases with histopathologically confirmed lymphoma exhibited no sonographic abnormalities. In the dogs with sonographic abnormalities, features including intestinal wall thickness and the presence or absence of wall layering were highly variable. Clinical signs pertaining to the gastrointestinal tract were also unreliable markers of gastrointestinal lymphoma, with weight loss, vomiting, and diarrhoea being uncommon presenting complaints; intestinal obstruction was not present in any patient. The sonographic appearance of gastrointestinal lymphoma in dogs is non-specific. Gastrointestinal lymphoma in dogs should be maintained as a differential diagnosis despite a sonographically normal appearing bowel.


Spc42p: a phosphorylated component of the S. cerevisiae spindle pole body (SPD) with an essential function during SPB duplication.
The 42-kD component of the S. cerevisiae spindle pole body (SPB) localizes to the electron-dense central plaque of the SPB. We have cloned the corresponding gene SPC42 (spindle pole component) and show that it is essential. Seven temperature-sensitive (ts) mutants in SPC42 were prepared by error-prone PCR. We found that a change to a proline residue in a potential coiled-coil region of Spc42p was responsible for the ts phenotype in at least three alleles, suggesting that formation of the coiled-coil is essential in normal function. The mutant cells showed a phenotype of predominantly single or bilobed SPBs often with an accumulation of unstructured electron-dense material associated with the bridge structure adjacent to the SPB. This phenotype suggests a defect in SPB duplication. This was confirmed by examining synchronized mutant cells that lose viability when SPB duplication is attempted. Spc42p is a phosphoprotein which shows some cell cycle-regulated phosphorylation. Overexpression of Spc42p causes the formation of a disc- or dome-shaped polymer composed of phosphorylated Spc42p, which is attached to the central plaque and associated with the outer nuclear membrane. Taken together, these data suggest that Spc42p forms a polymeric layer at the periphery of the SPB central plaque which has an essential function during SPB duplication and may facilitate attachment of the SPB to the nuclear membrane.


A Novel Window Technique Using CO2 Laser, and a Review of Methods for Nail Matrix Biopsy of Longitudinal Melanonychia.
Nail matrix histopathological examination is essential to diagnose longitudinal melanonychia (LM). Several methods for nail matrix biopsy have been introduced but are often difficult to perform because of their invasiveness and technical difficulty. Therefore, a less invasive and novel biopsy technique is needed. To introduce a window technique for nail matrix biopsy. We retrospectively reviewed the medical records and histopathological specimens of patients with LM who underwent the window technique for nail matrix biopsy at our institution between September 2015 and December 2016. Eleven cases from 10 patients with LM were subjected to our tailored window technique assisted by carbon dioxide (CO2) laser and dermoscopy. We performed nail plate dermoscopy to select the biopsy site and used CO2 laser to create the window in the proximal nail plate. Nail matrix pigmentation was carefully investigated using intraoperative dermoscopy. The technique established appropriate diagnosis in 11 LM cases, without significant complications, as follows: melanoma in situ (4 cases) and nail matrix activation (7 cases). The window technique assisted by CO2 laser and dermoscopy can be a minimally invasive and effective method for nail matrix LM biopsy under local anesthesia.


Helping and hindering: perceptions of enablers and barriers to collaboration within a rural South Australian mental health network.
To evaluate clinicians' perceptions of what helps and hinders the delivery of mental health care across a service network in a rural setting. Qualitative, semistructured interviews were conducted with 10 individuals who work in one rural mental health care service network. A regional centre in rural South Australia involving representatives of the mental health team, general practice, hospital, community health and nongovernment organisations. Clinicians' perceptions of barriers and enablers to working within their mental health care network were explored. Participants showed a strong shared commitment to effective mental health care delivery and a good understanding of the services that each offers. Interview data suggested that working relationships between local services could be perceived as stronger when a personal or historical element is recognisable. Similarly, the notion of familiarity and community involvement were perceived as facilitators in this network. A perceived barrier for participants was the failure to attract staff with mental health experience, leading to dependence upon the dedication and commitment of existing service providers. Collaboration is especially necessary in rural areas, where access to health care services is known to be difficult. The informality of relationships between service providers was shown to be the main facilitator in the network. This is both a strength as it promotes the communication between services and service providers that is essential for successful collaboration, yet is also a threat to the sustainability of the network based on the difficulties of staff recruitment and retention to rural settings.


Priming effect in a color discrimination task.
Two experiments were run to test whether the automatic coding of colors generates priming effects. Subjects were tachistoscopically presented a series of prime-target sequences. The prime stimulus could be either a red, green, or black circular dot, followed by a red or green annular ring (target). The role of automatic and conscious mechanisms was investigated in Exp. 1 by manipulating the predictive validity of the prime stimuli (80%, 50%, 20%), keeping constant the value of stimulus-onset asynchrony (350 msec.). Analysis showed priming effects even in the low predictive condition, where no conscious expectations could be activated. In Exp. 2, three different values of stimulus-onset asynchrony were used, 150, 350, and 2100 msec. Priming effects were obtained in the short and medium stimulus-onset asynchrony condition but not in the long one. Over-all, the data of both experiments produce converging evidence which indicates that the automatic elaboration of colored stimuli may produce priming effects.


Adenomatoid odontogenic tumour (adenoameloblastoma)--a review.
The adenomatoid odontogenic tumour (AOT) is a rare benign neoplasm of odontogenic origin. A review of the available published literature reports on AOT from Africa reveals that 33 cases appear to have been reported and that the tumour tends to occur in young patients, from 10-28 years with a mean age of 16.2 years. Females are affected more than males, with a female:male ratio of 3:2. 65.6% of cases were in the maxilla and 34.4% in the mandible, the majority of which (92.3%) are located in the anterior region of the jaws. 66.7% of the cases are associated with unerupted teeth. Clinically, AOT shows increasingly painless swellings which may eventually cause facial deformity. Tentative clinical diagnosis based on radiology is not pathognomonic for AOT; histopathological confirmation is necessary since incorrect diagnosis may lead to mutilating surgery whereas the lesion is benign with limited growth potential and treatment requires only simple surgical enucleation. Recurrence is rare.


Immune relevant genes of Japanese flounder, Paralichthys olivaceus.
The fish immune system is comprised of the non-specific and specific immune systems, having both humoral and cellular mechanisms to resist against infectious diseases. However, the biodefense- and immune-related systems of fish are not clearly understood at the molecular level. Characterization of the immune system of fish is important for the development of vaccines and other infectious disease prevention methods. In view of the above, we conducted an expressed sequence tags (ESTs) analysis of Japanese flounder, Paralichthys olivaceus for characterization of its immune system at the molecular level. We sequenced more than 7000 clones of 11 cDNA libraries. Numerous putative immune relevant genes, such as cytokines, cytokine receptors, cell surface molecules, transcription factors, complement component, anti-microbial proteins, proteases and protease inhibitors were identified. We also cloned and characterized several immune relevant genes from the BAC library. Currently the expression pattern for most of immune- and defense-related genes, from LPS or ConA/PMA treated peripheral blood leukocytes, after DNA vaccination study and after viral infection were characterized by microarray spotted with 1200 different Japanese flounder cDNAs. The expression patterns of these genes were varied in many of the genes examined, in different stimulations and time points. For the functional study of Japanese flounder's immune-relevant genes, we made recombinant proteins in insect cell system and characterized their activities. This review focuses on toll-like receptors, lysozymes, and T cell receptors of Japanese flounder and assessment of DNA vaccine using cDNA microarray of Japanese flounder.


Toward Digital Phenotypes of Early Childhood Mental Health via Unsupervised and Supervised Machine Learning.
Childhood mental health disorders such as anxiety, depression, and ADHD are commonly-occurring and often go undetected into adolescence or adulthood. This can lead to detrimental impacts on long-term wellbeing and quality of life. Current parent-report assessments for pre-school aged children are often biased, and thus increase the need for objective mental health screening tools. Leveraging digital tools to identify the behavioral signature of childhood mental disorders may enable increased intervention at the time with the highest chance of long-term impact. We present data from 84 participants (4-8 years old, 50% diagnosed with anxiety, depression, and/or ADHD) collected during a battery of mood induction tasks using the ChAMP System. Unsupervised Kohonen Self-Organizing Maps (SOM) constructed from movement and audio features indicate that age did not tend to explain clusters as consistently as gender within task-specific and cross-task SOMs. Symptom prevalence and diagnostic status also showed some evidence of clustering. Case studies suggest that high impairment (>80th percentile symptom counts) and diagnostic subtypes (ADHD-Combined) may account for most behaviorally distinct children. Based on this same dataset, we also present results from supervised modeling for the binary classification of diagnoses. Our top performing models yield moderate but promising results (ROC AUC .6-.82, TPR .36-.71, Accuracy .62-.86) on par with our previous efforts for isolated behavioral tasks. Enhancing features, tuning model parameters, and incorporating additional wearable sensor data will continue to enable the rapid progression towards the discovery of digital phenotypes of childhood mental health.Clinical Relevance- This work advances the use of wearables for detecting childhood mental health disorders.


Reevaluating the role of LTD in cerebellar motor learning.
Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.


Identification of a CYP84 family of cytochrome P450-dependent mono-oxygenase genes in Brassica napus and perturbation of their expression for engineering sinapine reduction in the seeds.
CYP84 is a recently identified family of cytochrome P450-dependent mono-oxygenases defined by a putative ferulate-5-hydroxylase (F5H) from Arabidopsis. Until recently F5H has been thought to catalyze the hydroxylation of ferulate to 5-OH ferulate en route to sinapic acid. Sinapine, a sinapate-derived ester in the seeds, is antinutritional and a target for elimination in canola meal. We have isolated three F5H-like genes (BNF5H1-3) from a cultivated Brassica napus, whose amphidiploid progenitor is considered to have arisen from a fusion of the diploids Brassica rapa and Brassica oleracea. Two cultivated varieties of the diploids were also found to contain BNF5H3 and additionally either BNF5H1 or BNF5H2, respectively. Whereas all three are >90% identical in their coding sequence, BNF5H1 and BNF5H2 are closer to each other than to BNF5H3. This and additional data suggest that the two groups of genes have diverged in an ancestor of the diploids. B. napus showed maximal F5H expression in the stems, least in the seeds, and subtle differences among the expression profiles of the three genes elsewhere. Transgenic B. napus with cauliflower mosaic virus 35S-antisense BNF5H contained up to 40% less sinapine, from 9.0 +/- 0.3 mg in the controls to 5.3 +/- 0.3 mg g(-1) seed. F5H from Arabidopsis and a similar enzyme from sweetgum (Liquidamber styraciflua) has recently been shown to have coniferaldehyde hydroxylase activity instead of F5H activity. Thus the supply of 5-OH coniferaldehyde or 5-OH ferulate has a bearing on sinapine accumulation in canola seeds.


Scanning electron microscope study of ancient parasite eggs recovered from Korean mummies of the Joseon Dynasty.
We have previously shown that parasite eggs have been identified in the coprolites of Korean mummies. These eggs have shed light on parasitic infection patterns in Korean populations living several hundred years ago. We conducted a scanning electron microscopy (SEM) study on ancient Trichuris trichiura, Ascaris lumbricoides, Metagonimus yokogawai, Paragonimus westermani, and Gymnophalloides seoi eggs recovered from Korean mummies of the Joseon Dynasty. We anticipated that the taphonomic conditions of mummification would alter the eggs of certain species but not of others. Our SEM data show that each species of ancient egg exhibited different degrees of preservation. Thus, some of them, for example, M. yokogawai, exhibited a better preservation status than others, suggesting that they should be the first candidates considered when choosing subjects for future paleoparasitological studies.


In vitro modeling of cranial placode differentiation: Recent advances, challenges, and perspectives.
Cranial placodes are transient ectodermal thickenings that contribute to a diverse array of organs in the vertebrate head. They develop from a common territory, the pre-placodal region that over time segregates along the antero-posterior axis into individual placodal domains: the adenohypophyseal, olfactory, lens, trigeminal, otic, and epibranchial placodes. These placodes terminally differentiate into the anterior pituitary, the lens, and contribute to sensory organs including the olfactory epithelium, and inner ear, as well as several cranial ganglia. To study cranial placodes and their derivatives and generate cells for therapeutic purposes, several groups have turned to in vitro derivation of placodal cells from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs). In this review, we summarize the signaling cues and mechanisms involved in cranial placode induction, specification, and differentiation in vivo, and discuss how this knowledge has informed protocols to derive cranial placodes in vitro. We also discuss the benefits and limitations of these protocols, and the potential of in vitro cranial placode modeling in regenerative medicine to treat cranial placode-related pathologies.


Striatal xenotransplantation of human retinal pigment epithelial cells attached to microcarriers in hemiparkinsonian rats ameliorates behavioral deficits without provoking a host immune response.
Attachment of donor cells to microcarriers has been reported to make them more tolerable for transplantation into the brain. Human retinal pigment epithelial (hRPE) cells have been previously reported to contain enzymes for the production of dopa. Therefore, we examined the host immune response and behavioral effects of xenotransplantation of hRPE cells attached to microcarriers (hRPE-M) into the striatum of unilateral dopamine-depleted rats. Thirty-four adult rats were lesioned with 6-OHDA injections into the medial forebrain bundle on the right side. After 5 weeks of testing for apomorphine-induced rotations (AIR), animals were randomized for right striatal surgery into the following four groups: hRPE-M (group 1), hRPE alone (group 2), microcarriers alone (group 3), or needle tract alone (group 4). Following surgery, animals were tested for AIR every 4 weeks for a period of 12-18 weeks and thereafter euthanized. There was a significant reduction in AIR scores posttransplantation in all groups of animals in the initial observation points at 4 weeks and 8 weeks. However, there was a gradual return to baseline scores in groups 2, 3, and 4 animals at 12 weeks and at 18 weeks only group 1 animals had statistically significant (p = 0.001, repeated measures ANOVA, means comparison, predetermined contrasts) reduction in AIR scores. Brain tissue from representative animals from each group was cut into 30-microm coronal sections, stained for cresyl violet, tyrosine hydroxylase (TH), and markers for host immune activation. Sections through the striatum from group 1 animals revealed microcarriers with attached cells resembling RPE cells. No evidence of transplanted hRPE cells could be detected in sections from group 2 animals while those from groups 3 and 4 animals showed microcarriers and a needle tract alone, respectively. There was no host TH-immunoreactive sprouting response in the striatum in any of the groups and the host immune response was minimal. These results suggest that intrastriatal hRPE-M xenotransplantation into rats is well tolerated without systemic immunosuppression and that such transplants may provide behavioral benefit for parkinsonism.


Antibodies to the Plasmodium falciparum antigens circumsporozoite protein, thrombospondin-related adhesive protein, and liver-stage antigen 1 vary by ages of subjects and by season in a highland area of Kenya.
Immunoglobulin G (IgG) antibodies to three vaccine candidate preerythrocytic Plasmodium falciparum antigens were evaluated in children and adults in an epidemic-prone highland area of Kenya during rainy (high-transmission) and dry (low-transmission) seasons. The frequencies and median levels of IgG antibodies to circumsporozoite protein (CSP) and thrombospondin-related adhesive protein (TRAP) were compared to the frequencies and median levels of IgG antibodies to liver-stage antigen 1 (LSA-1) reported previously. The frequencies and median levels of IgG antibodies to CSP and TRAP were similar in children and adults in the rainy season, but they were lower in children than in adults in the dry season. The frequencies and median levels of antibodies to LSA-1 were lower in children than in adults in both the rainy and dry seasons. Antibodies to CSP and LSA-1 were primarily members of the IgG1 and IgG3 subclasses, while antibodies to TRAP were primarily members of the IgG3 and IgG4 subclasses. In a treatment-reinfection study following dry season testing, antibodies to TRAP were associated with a trend toward protection from infection in children (P = 0.051) but not in adults. Antibodies to LSA-1 and CSP did not correlate with protection in children or adults. In this highland area of Kenya with unstable transmission, IgG antibodies to preerythrocytic P. falciparum antigens vary in subjects by age and season, and the protective effects of these antibodies against infection may be different in adults and children.


Genetic Variation of Bordetella pertussis in Austria.
In Austria, vaccination coverage against Bordetella pertussis infections during infancy is estimated at around 90%. Within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunity and vaccine coverage. Waning immunity in the host and/or adaptation of the bacterium to the immunised hosts could contribute to the observed re-emergence of pertussis. In this study we therefore addressed the genetic variability in B. pertussis strains from several Austrian cities. Between the years 2002 and 2008, 110 samples were collected from Vienna (n = 32), Linz (n = 63) and Graz (n = 15) by nasopharyngeal swabs. DNA was extracted from the swabs, and bacterial sequence polymorphisms were examined by MLVA (multiple-locus variable number of tandem repeat analysis) (n = 77), by PCR amplification and conventional Sanger sequencing of the polymorphic regions of the prn (pertactin) gene (n = 110), and by amplification refractory mutation system quantitative PCR (ARMS-qPCR) (n = 110) to directly address polymorphisms in the genes encoding two pertussis toxin subunits (ptxA and ptxB), a fimbrial adhesin (fimD), tracheal colonisation factor (tcfA), and the virulence sensor protein (bvgS). Finally, the ptxP promoter region was screened by ARMS-qPCR for the presence of the ptxP3 allele, which has been associated with elevated production of pertussis toxin. The MLVA analysis revealed the highest level of polymorphisms with an absence of MLVA Type 29, which is found outside Austria. Only Prn subtypes Prn1/7, Prn2 and Prn3 were found with a predominance of the non-vaccine type Prn2. The analysis of the ptxA, ptxB, fimD, tcfA and bvgS polymorphisms showed a genotype mixed between the vaccine strain Tohama I and a clinical isolate from 2006 (L517). The major part of the samples (93%) displayed the ptxP3 allele. The consequences for the vaccination strategy are discussed.


High-Value, Cost-Conscious Care: Iterative Systems-Based Interventions to Reduce Unnecessary Laboratory Testing.
Inappropriate testing contributes to soaring healthcare costs within the United States, and teaching hospitals are vulnerable to providing care largely for academic development. Via its "Choosing Wisely" campaign, the American Board of Internal Medicine recommends avoiding repetitive testing for stable inpatients. We designed systems-based interventions to reduce laboratory orders for patients admitted to the wards at an academic facility. We identified the computer-based order entry system as an appropriate target for sustainable intervention. The admission order set had allowed multiple routine tests to be ordered repetitively each day. Our iterative study included interventions on the automated order set and cost displays at order entry. The primary outcome was number of routine tests controlled for inpatient days compared with the preceding year. Secondary outcomes included cost savings, delays in care, and adverse events. Data were collected over a 2-month period following interventions in sequential years and compared with the year prior. The first intervention led to 0.97 fewer laboratory tests per inpatient day (19.4%). The second intervention led to sustained reduction, although by less of a margin than order set modifications alone (15.3%). When extrapolating the results utilizing fees from the Centers for Medicare and Medicaid Services, there was a cost savings of $290,000 over 2 years. Qualitative survey data did not suggest an increase in care delays or near-miss events. This series of interventions targeting unnecessary testing demonstrated a sustained reduction in the number of routine tests ordered, without adverse effects on clinical care.


Optimization of volar percutaneous screw fixation for scaphoid waist fractures using traction, positioning, imaging, and an angiocatheter guide.
Percutaneous screw fixation of nondisplaced or reducible scaphoid fractures has become more popular as techniques and implants have improved. Many authors have advocated for the dorsal approach, citing difficulties with adequate screw placement from the volar approach. We have developed a straightforward and reproducible technique for volar percutaneous scaphoid screw fixation that mitigates most of the drawbacks of the approach. The wrist is held in extension and ulnar deviation with traction through the thumb. A 14-gauge angiocatheter needle is then used to localize the starting point and as a cannula for the guide wire. Specific fluoroscopic views help to confirm optimal guide wire placement.


Suicidal Ideation Is Associated with Altered Variability of Fingertip Photo-Plethysmogram Signal in Depressed Patients.
Physiological and psychological underpinnings of suicidal behavior remain ill-defined and lessen timely diagnostic identification of this subgroup of patients. Arterial stiffness is associated with autonomic dysregulation and may be linked to major depressive disorder (MDD). The aim of this study was to investigate the association between arterial stiffness by photo-plethysmogram (PPG) in MDD with and without suicidal ideation (SI) by applying multiscale tone entropy (T-E) variability analysis. Sixty-one 10-min PPG recordings were analyzed from 29 control, 16 MDD patients with (MDDSI+) and 16 patients without SI (MDDSI-). MDD was based on a psychiatric evaluation and the Mini-International Neuropsychiatric Interview (MINI). Severity of depression was assessed using the Hamilton Depression Rating Scale (HAM-D). PPG features included peak (systole), trough (diastole), pulse wave amplitude (PWA), pulse transit time (PTT) and pulse wave velocity (PWV). Tone (Diastole) at all lags and Tone (PWA) at lags 8, 9, and 10 were found to be significantly different between the MDDSI+ and MDDSI- group. However, Tone (PWA) at all lags and Tone (PTT) at scales 3-10 were also significantly different between the MDDSI+ and CONT group. In contrast, Entropy (Systole), Entropy (Diastole) and Tone (Diastole) were significantly different between MDDSI- and CONT groups. The suicidal score was also positively correlated (r = 0.39 ~ 0.47; p < 0.05) with systolic and diastolic entropy values at lags 2-10. Multivariate logistic regression analysis and leave-one-out cross-validation were performed to study the effectiveness of multi-lag T-E features in predicting SI risk. The accuracy of predicting SI was 93.33% in classifying MDDSI+ and MDDSI- with diastolic T-E and lag between 2 and 10. After including anthropometric variables (Age, body mass index, and Waist Circumference), that accuracy increased to 96.67% for MDDSI+/- classification. Our findings suggest that tone-entropy based PPG variability can be used as an additional accurate diagnostic tool for patients with depression to identify SI.


Action potential bursts enhance transmitter release at a giant central synapse.
Patterns of action potentials (APs), often in the form of bursts, are critical for coding and processing information in the brain. However, how AP bursts modulate secretion at synapses remains elusive. Here, using the calyx of Held synapse as a model we compared synaptic release evoked by AP patterns with a different number of bursts while the total number of APs and frequency were fixed. The ratio of total release produced by multiple bursts to that by a single burst was defined as 'burst-effect'.We found that four bursts of 25 stimuli at 100 Hz increased the totalcharge of EPSCs to 1.47 ± 0.04 times that by a single burst of 100 stimuli at the same frequency.Blocking AMPA receptor desensitization and saturation did not alter the burst-effect, indicating that it was mainly determined by presynaptic mechanisms. Simultaneous dual recordings of presynaptic membrane capacitance (Cm) and EPSCs revealed a similar burst-effect, being 1.58±0.13by Cm and 1.49±0.05 by EPSCs. Reducing presynapticCa2+ influx by lowering extracellular Ca2+concentration or buffering residual intracellular Ca2+ with EGTA inhibited the burst-effect. We further developed a computational model largely recapitulating the burst-effect and demonstrated that this effect is highly sensitive to dynamic change in availability of the releasable pool of synaptic vesicles during various patterns of activities. Taken together, we conclude that AP bursts modulate synaptic output mainly through intricate interaction between depletion and replenishment of the large releasable pool. This burst-effect differs from the somatic burst-effect previously described from adrenal chromaffin cells, which substantially depends on activity-induced accumulation of Ca2+ to facilitate release of a limited number of vesicles in the releasable pool. Hence, AP bursts may play an important role in dynamically regulating synaptic strength and fidelity during intense neuronal activity at central synapses.


Effect of sacrospinous hysteropexy with graft vs vaginal hysterectomy with uterosacral ligament suspension on treatment failure in women with uterovaginal prolapse: 5-year results of a randomized clinical trial.
Vaginal hysterectomy with suture apical suspension is commonly performed for uterovaginal prolapse. Sacrospinous hysteropexy with graft (vaginal mesh hysteropexy) is an alternative, although in 2019 the Food and Drug Administration removed this mesh product from the United States market. Our objective was to compare the efficacy and adverse events of these 2 procedures. At 9 clinical sites in the United States National Institutes of Health and National Institute of Child Health and Human Development Pelvic Floor Disorders Network, 183 postmenopausal women requesting vaginal surgery for symptomatic uterovaginal prolapse were enrolled in a multisite randomized superiority clinical trial, comparing a sacrospinous hysteropexy with graft (hysteropexy) with a vaginal hysterectomy with uterosacral ligament suspension (hysterectomy). Participants consented to remain masked to treatment assignment for the study duration. Study visits were conducted at 6-month intervals through 60 months. The primary treatment failure composite outcome (retreatment of prolapse, prolapse beyond the hymen, or prolapse symptoms) was evaluated with survival modeling. Secondary outcomes included complications or adverse events, individual anatomic measures of the pelvic organ prolapse quantification examination, and presence, severity, and impact and bother of prolapse, urinary, bowel, and pain symptoms as measured by validated questionnaires. The 3-year published results suggested better primary outcomes with sacrospinous hysteropexy with graft, but the differences were not statistically significant (P=.06). This study reports the 5-year outcomes. A total of 183 women with a mean age of 66 years were randomized between April 2013 and February 2015; 93 were randomized to hysteropexy and 90 were randomized to hysterectomy. Notably, 175 were included in the trial, and 156 (89%) completed the 5-year follow-up. The primary outcome showed fewer failures for hysteropexy than hysterectomy through 5 years (adjusted hazard ratio, 0.58; 95% confidence interval, 0.36-0.94; P=.03), with failure rates of 37% vs 54%, respectively, resulting in a difference of -18% (95% confidence interval, -33% to -3%) at 5 years. With the exception of the Urogenital Distress Inventory, no group differences were demonstrated in patient-reported pelvic floor symptoms, prolapse symptoms, bowel function symptoms, general quality of life, body image, or pelvic pain. At their last visit through 5 years, 70% of participants (129 of 183) reported they remained masked to their treatment with no difference in masking between groups. Adverse events for hysteropexy vs hysterectomy included mesh exposure (8% vs 0%), granulation tissue after 12 weeks (1% vs 12%), and suture exposure after 12 weeks (3% vs 21%), respectively. Among women with symptomatic uterovaginal prolapse undergoing vaginal surgery, sacrospinous hysteropexy with graft resulted in a lower composite failure rate than vaginal hysterectomy through 5 years. There were no meaningful differences in patient-reported outcomes between groups. Our results suggest that this vaginal mesh hysteropexy procedure should be made available to patients.


Simultaneous determination of aerosol optical thickness and exponent of Junge power law from satellite measurements of two near-infrared bands over the ocean.
An iterative algorithm is presented in this study for simultaneous determination of both the aerosol optical thickness and the exponent of the Junge power law from the total reflectance data of two satellite-based, near-infrared bands over the ocean. The atmospheric aerosol model is assumed as the Junge power-law size distribution in retrieval of the data. Numerical simulations show that relative errors in retrieval of the aerosol optical thickness and the exponent of the Junge power law are less than 5% when the actual atmospheric aerosol follows the Junge power-law size distribution. For other aerosol size distributions, relative errors of the aerosol optical thickness are less than approximately 10%. The proposed method is applied to a case study of the data of two near-infrared channels of the Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) over the East China Sea area. The results show that reasonable spatial distribution of the exponent of the Junge law and the aerosol optical thickness may be obtained on a pixel-by-pixel basis through use of the proposed retrieval algorithm.


[The evolution of adenoidectomy].
The critical analysis of publications concerning methods designed for the surgical treatment of adenoids is presented. Various surgical techniques are considered with special reference to their indications for use, invasiveness, effectiveness, and safety. Recent developments in this field give evidence that evolution of adenoidectomy brought about highly efficacious (up to 99%) mini-invasive and safe surgical procedures producing the minimal risk of relapses and postoperative complications. All these advancements became possible due to the introduction of endoscopic intraoperative control, general anesthesia, and the use of modern surgical instruments. Modern approaches make unnecessary radical removal of the lymphoid tissue.


Stressors, needs, and resources: what AIDS home caregivers have to say.
Caregivers of persons with AIDS often face psychological, physical, economic, and social barriers to effective care. Community resources and support are inadequate. How can home care professionals help caregivers deal with the implications of caring for a friend or loved one who has this socially stigmatized disease?


Identification of the Arabidopsis palmitoyl-monogalactosyldiacylglycerol delta7-desaturase gene FAD5, and effects of plastidial retargeting of Arabidopsis desaturases on the fad5 mutant phenotype.
Hexadeca 7,10,13-trienoic acid (16:3Delta(7,10,13)) is one of the most abundant fatty acids in Arabidopsis (Arabidopsis thaliana) and a functional component of thylakoid membranes, where it is found as an sn-2 ester of monogalactosyldiacylglycerol. The Arabidopsis fad5 mutant lacks activity of the plastidial palmitoyl-monogalactosyldiacylglycerol Delta7-desaturase FAD5, and is characterized biochemically by the absence of 16:3Delta(7,10,13) and physiologically by reduced chlorophyll content and a reduced recovery rate after photoinhibition. While the fad5 mutation has been mapped, the FAD5 gene was not unambiguously identified, and a formal functional characterization by complementation of fad5 mutant phenotypes has not been reported. Two candidate genes (At3g15850 and At3g15870) predicted to encode plastid-targeted desaturases at the fad5 chromosomal locus were cloned from fad5 plants and sequenced. A nonsense mutation changing codon TGG (Trp-98) into TGA (stop) was identified in At3g15850 (ADS3), whereas the fad5 At3g15870 allele was identical to wild type (after correction of a sequencing error in the published wild-type genomic At3g15870 sequence). Expression of a genomic clone or cDNA for wild-type At3g15850 conferred on fad5 plants the ability to synthesize 16:3Delta(7,10,13) and restored leaf chlorophyll content. Arabidopsis carrying a T-DNA insertion in At3g15870 had wild-type levels of both 16:3Delta(7,10,13) and chlorophyll. Together, these data formally prove that At3g15850 is FAD5. Interestingly, the fad5 phenotype was partially complemented when extraplastidial Delta9-desaturases of the Arabidopsis desaturase (ADS) family were expressed as fusions with a plastidial transit peptide. Tight correlation between leaf 16:3Delta(7,10,13) levels and chlorophyll content suggests a role for plastidial fatty acid desaturases in thylakoid formation.


Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey.
This study evaluated the effect of repeated photodynamic therapy (PDT) applications on normal primate retina and choroid using an intravenous infusion of liposomal benzoporphyrin derivative (verteporfin). This was an experimental study in a primate model. ANIMALS/CONTROLS: Six cynomolgus monkeys were used as experimental subjects and one monkey was used as a control subject. Three consecutive PDT treatments at 2-week intervals were applied over the center of the fovea or the optic nerve of each eye. Verteporfin was delivered by intravenous infusion at a dose of 6 mg/m2, 12 mg/m2, or 18 mg/m2. Laser irradiation was then applied using a diode laser (689 nm) with light doses and spot sizes kept constant. Findings were documented by fundus photography, fluorescein angiography, and light and electron microscopy. A cumulative dose response was seen angiographically and histologically with more severe damage to the retina and choroid noted at higher dye doses. Photodynamic therapy applied to the macula using the 6-mg/m2 verteporfin dose showed recovery of choriocapillaris, with mild retinal pigment epithelium and outer photoreceptor damage at 6 weeks. At this dose, the optic nerve showed few focal sites of axon atrophy and capillary loss. Treatments over the macula using the 12-mg/m2 and 18-mg/m2 doses led to chronic absence of choriocapillaris and photoreceptors at 6 weeks. One of two optic nerves became atrophic after PDT applications using dye doses of 12 mg/m2, and both optic nerves became atrophic in the 18-mg/m2 dye dose group. Limited damage to the retina, choroid, and optic nerve was present in primates treated with multiple PDT sessions using 6 mg/m2 verteporfin with light doses and the timing of irradiation kept constant. However, PDT using higher dye doses of 12 mg/m2 and 18 mg/m2 led to significant chronic damage to the normal retina, choroid, and optic nerve.


Performance of tumor testing for Lynch syndrome identification in patients with colorectal cancer: A retrospective single-center study.
To investigate the performance of tumor testing approaches in the identification of Lynch syndrome (LS) in a single-center cohort of people with colorectal cancer (CRC). A retrospective analysis of data stored in a dedicated database was carried out to identify patients with CRC suspected for LS who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, between 1999 and 2014. The sensitivity and specificity of immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis (alone or combined) were calculated with respect to the presence of causative MMR germline variants. A total of 683 patients with CRC suspected for LS were identified. IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features. Univariate and multivariate analysis revealed a significant correlation of pathogenic MMR germline variants with all clinicopathologic features including Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset, stage, and grade. The highest odds ratio values were observed for IHC and MSI (17.1 and 8.8, respectively). The receiver operating characteristic curve and area under the curve values demonstrated that IHC alone or combined with other clinicopathologic parameters was an excellent test for LS identification. This study confirms the effectiveness of tumor testing to identify LS among patients with CRC. Although IHC and MSI analysis were similarly effective, IHC could be a better strategy for LS identification as it is less expensive and more feasible.


PD-1/PD-L1 and VEGF-A/VEGF-C expression in lymph node microenvironment and association with melanoma metastasis and survival.
Regional lymph nodes are affected frequently by melanoma metastasis. Its microenvironment may be associated with tumor progression. We investigated sentinel nodes with and without tumor and negative nodes surrounding positive nodes, looking for patterns related to tumor immune interaction and lymphovascular progression. We quantified programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1, vascular endothelial growth factor (VEGF)-A/VEGF-C expressions in lymph nodes of 103 patients who underwent sentinel lymph node biopsy. Two groups were studied: negative sentinel lymph nodes and positive ones. Negative lymph nodes of sequential lymphadenectomy from positive cases were also studied. Markers were assessed by immunohistochemistry. Results were related to clinical/histological outcomes. VEGF-A/VEGF-C analysis showed higher positivity in metastatic nodes and higher positivity in the surrounding negative nodes from positive cases in comparison with nonmetastatic patients. Programmed cell death-ligand 1, studied only in metastasis, presented high positivity, not associated with prognosis. PD-1 expressions were similar in the groups with a 1% cutoff and higher in the metastasis with a 5% cutoff. Higher VEGF-A expression was related to higher pathological stages. PD-1 expression in the lymph node was associated with higher survival. Other clinical and histopatological variables were not associated with marker expression patterns. VEGF-A and VEGF-C expressions in lymph nodes were associated with the presence of lymph node metastasis. PD-1 expression in the lymph node was related to higher survival rates and this should be explored in the context of adjuvant immunotherapy.


Electroencephalographic correlates of prenatal exposure to alcohol in infants and children: a review of findings and implications for neurocognitive development.
In this paper, we reviewed all existing studies using electroencephalography (EEG) in infants and children with known prenatal exposure to alcohol (PEA). The guiding purposes of the review were to determine if (1) EEG is a useful neuroimaging technique for investigating the brain correlates of PEA in infants and children, (2) there are indeed consistent EEG correlates of PEA in literature, and (3) these EEG correlates can be framed within a coherent picture of emerging implications for the study of PEA and its effects. The review confirms that EEG techniques have proven useful in indicating evidence of differential effects of patterns of PEA and timing in early fetal development and impairment of brain maturation in older children. In general, these techniques could be important in functional assessment of the brain of children affected by PEA, especially if used in conjunction with other neuroimaging techniques. The reviewed studies also suggest that although the impact on sensory and cognitive functions may involve extensive neural networks, there are EEG correlates of PEA which may in the future lead to the identification of neurophysiologic markers. A consistent aspect that emerges from the EEG data is that converging evidence from the study of different systems and processes suggests that PEA may almost invariably have consequences for later neurocognitive development.


[Nutritional Support for Patients with Pancreatic Cancer].
Pancreatic cancer is the ninth common malignancy in South Korea. It has a dismal prognosis with a 5-year overall survival rate of less than 10%, and pancreatic cancer is associated with cancer cachexia, which is defined as the loss of muscle mass that is not reversible by conventional nutritional support. Cachexia is noted in over 85% of all pancreatic cancer patients and it is strongly related with the disease's mortality. Nearly 30% of pancreatic cancer deaths are due to cachexia rather than being due to the tumor burden. Therefore, it is crucial to discover the mechanisms behind the development of muscle wasting in pancreatic cancer patients and find novel therapeutics for targeting cachexia. This review deals with the current understanding about the development of cachexia and nutritional support in those patients suffering with pancreatic cancer.


Impact of interprofessional collaboration on chronic disease management: Findings from a systematic review of clinical trial and meta-analysis.
Improvement of chronic disease management demands effective collaborative relationships between health and social-care which is achieved through teamwork. Interprofessional Education (IPE) and Interprofessional Collaboration (IPC) are recognized as essential for the delivery of effective and efficient healthcare. Although IPC and IPE are key components of primary care, evidence of studies evaluating how an IPE intervention prior to IPC improved chronic patient outcomes remains scarce. The aim of this study was to assess the impact of IPC interventions on the management of chronic patients compared to usual care. A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) on IPC interventions on chronicity management and their impact on clinical and process outcomes was conducted. Of the 11,128 papers initially retrieved, 23 met the inclusion criteria. Meta-analyses results showed the reduction of systolic blood pressure (Mean Difference (MD) -3.70; 95 % CI -7.39, -0.01), glycosylated hemoglobin (MD -0.20; 95 % CI -0.47, -0.07), LDL cholesterol (MD -5.74; 95 % CI -9.34, -2.14), diastolic blood pressure (MD -1.95; 95 % CI -3.18, -0.72), days of hospitalization (MD -2.22; 95 % CI -4.30, -0.140). A number of positive findings for outcomes related to IPC were found reflecting an improvement of quality of care and an enhancement in the delivery of patient-centered and coordinated care. Moreover, the need for a purposeful systemic approach linking interprofessional education with interprofessional collaboration and patient health and wellbeing is necessary.


Mach cone induced by γ-triggered jets in high-energy heavy-ion collisions.
Medium excitation by jet shower propagation inside a quark-gluon plasma is studied within a linear Boltzmann transport and a multiphase transport model. Contrary to the naive expectation, it is the deflection of both the jet shower and the Mach-cone-like excitation in an expanding medium that is found to give rise to a double-peak azimuthal particle distribution with respect to the initial jet direction. Such a deflection is the strongest for hadron-triggered jets which are often produced close to the surface of a dense medium due to trigger bias and travel against or tangential to the radial flow. Without such trigger bias, the effect of deflection on γ-jet showers and their medium excitation is weaker. Comparative study of hadron and γ-triggered particle correlations can therefore reveal the dynamics of jet-induced medium excitation in high-energy heavy-ion collisions.


Response, use and habituation to a mouse house in C57BL/6J and BALB/c mice.
Animal welfare depends on the possibility to express species-specific behaviours and can be strongly compromised in socially and environmentally deprived conditions. Nesting materials and refuges are very important resources to express these behaviours and should be considered as housing supplementation items. We evaluated the effects of one item of housing supplementation in standard settings in laboratory mice. C57BL/6JOlaHsd (B6) and BALB/cOlaHsd (BALB) young male and female mice, upon arrival, were housed in groups of four in standard laboratory cages and after 10 days of acclimatization, a red transparent plastic triangular-shaped Mouse House™ was introduced into half of the home cages. Animals with or without a mouse house were observed in various contexts for more than one month. Body weight gain and food intake, home cage behaviours, emotionality and response to standard cage changing procedures were evaluated. The presence of a mouse house in the home cage did not interfere with main developmental and behavioural parameters or emotionality of BALB and B6 male and female mice compared with controls. Both strains habituated to the mouse house in about a week, but made use of it differently, with BALB mice using the house more than the B6 strain. Our results suggest that mice habituated to the mouse house rather quickly without disrupting their home cage activities. Scientists can thus be encouraged to use mouse houses, also in view of the implementation of the EU Directive (2010/63/EU).


Ultrasonic assessment of cardiovascular geometry and function in the human fetus.
A new technique of studying fetal cardiac geometry and function from two-dimensional real-time images is presented. A significant increase in left ventricular size with advancing gestational age was observed. Left ventricular cardiac output size with advancing gestational age was observed. Left ventricular cardiac output (LVCO) was 210 +/- 48 ml/min (Mean +/- 1 SD) between 27 and 33 weeks and 336 +/- 35 ml/min between 34 and 41 weeks gestation. Blood flow (mean flow) in the descending aorta during these two periods was 365 +/- 80 and 490 +/- 65 ml/min. In four fetuses, the LVCO per kg birth weight ranged between 114 and 123 ml/kg/min and the blood flow in the descending aorta between 168 ad 179 ml/kg/min. If total cardiac output is considered to be twice the LVCO, the proportion of total cardiac output being distributed through the descending aorta and placenta is about 75% and 45% respectively.


[Degeneration of ponto-cerebellar tract visualized by diffusion tensor imaging in multiple system atrophy].
We visualized ponto-cerebellar tracts projecting through the middle cerebellar peduncle of 3 patients with early stage multiple system atrophy (MSA), 3 patients with advanced stage MSA, and a healthy control using diffusion tensor imaging (DTI) on 1.5T magnetic resonance imaging (MRI). We also examined whether the location of the degenerated ponto-cerebellar tracts coincided with that of the transverse part of the so-called "hot cross bun sign (HCB)" on MRI. DTI successfully demonstrated the degeneration of ponto-cerebellar tracts in MSA patients. The tracts in advanced stage MSA patients appeared more sparse than those in patients of the early stage. High apparent diffusion coefficient (ADC) values and low fractional anisotropy (FA) values also indicated the degeneration of the ponto-cerebellar tracts in MSA patients. The tracts in the ventral pons were more sparse than those in the central pons. The location of the degenerated ponto-cerebellar tracts of the central pons appeared to coincide with that of the transverse part of HCB. Visualization of degenerated ponto-cerebellar tracts that cross the ventral pons using DTI might be useful for the early diagnosis.


Parental permission and perceived research benefits in adolescent STI research.
An understanding of why parents provide consent for adolescent participation in research on sensitive topics can inform and improve the ethical conduct and review of such research. As part of a longitudinal study of sexually transmitted infections (STIs) in lower-income adolescents, we asked 134 parents why they permitted their daughter to participate, analyzing responses using qualitative methods. Over half described participation benefits, providing reasons such as the study being generally good for their daughters, sex education, someone to talk to, and STI testing. Other reasons included positive interactions and familiarity with research and clinical staff, friend or family member participation, and adolescent autonomy in making the decision to participate. If parents perceived their daughter to be "at risk" in some way, such as for STI or pregnancy, they were more likely to cite participation benefits. These data can be used to make such research more sensitive to family and community needs.


A computational study identifies HIV progression-related genes using mRMR and shortest path tracing.
Since statistical relationships between HIV load and CD4+ T cell loss have been demonstrated to be weak, searching for host factors contributing to the pathogenesis of HIV infection becomes a key point for both understanding the disease pathology and developing treatments. We applied Maximum Relevance Minimum Redundancy (mRMR) algorithm to a set of microarray data generated from the CD4+ T cells of viremic non-progressors (VNPs) and rapid progressors (RPs) to identify host factors associated with the different responses to HIV infection. Using mRMR algorithm, 147 gene had been identified. Furthermore, we constructed a weighted molecular interaction network with the existing protein-protein interaction data from STRING database and identified 1331 genes on the shortest-paths among the genes identified with mRMR. Functional analysis shows that the functions relating to apoptosis play important roles during the pathogenesis of HIV infection. These results bring new insights of understanding HIV progression.


Synthetic spectroscopic models related to coenzymes and base pairs. VII. Stacking interactions in tRNA; the "bend" at dimethylguanosine.
We have examined the stacking interactions of N(2)-dimethyl-guanosine with the nucleosides, e.g., adenosine and cytidine, found adjacent to it in certain tRNA's, by the use of model compounds in which the trimethylene bridge was substituted for the ribose-phosphate-ribose linkage. From the hypochromism exhibited by synthetic 9-[3-(aden-9-yl)propyl]-2-dimethylaminopurine-6-one (IV) and by 9-[3-(cytos-1-yl)propyl]2-dimethylaminopurin-6-one in aqueous solution (VI) it is appearent that the interaction is at least as great between the N(2)-dimethylguanine moiety and adenine or cytosine as between guanine and these two bases. The fluorescence and phosphorescence emission spectra were obtained in ethylene glycol-water glass at 80 degrees K. The exciplex fluorescence observed for both bi-molecules (IV and VI) containing the N(2)-dimethylguanine unit provides further evidence for stacked chromophores.


Phosphatidylinositol 3-kinase and focal adhesion kinase are early signals in the growth factor-like responses to thrombospondin-1 seen in human vascular smooth muscle.
Thrombospondin-1 (TSP-1) is a matricellular protein that is expressed in negligible amounts in normal blood vessels but is markedly upregulated in vascular injury. Although TSP-1 can act as a pleiotropic regulator for human vascular smooth muscle cells (HVSMCs), the intracellular signaling pathways stimulated by this protein remain obscure. In cultured HVSMCs derived from saphenous vein, TSP-1 induces tyrosine phosphorylation of a number of cellular proteins, with a complex temporal pattern of activation. Immunoprecipitation techniques have identified the early tyrosine-phosphorylated signals as being the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-K) and focal adhesion kinase (FAK). Tyrosine phosphorylation of the p85 subunit of PI 3-K showed a biphasic response to TSP-1 stimulation, which corresponded to a biphasic activation of the lipid kinase. Treatment with both wortmannin and LY294002 inhibited PI 3-K activity of HVSMCs but did not affect tyrosine phosphorylation of the p85 regulatory subunit. TSP-1-stimulated FAK phosphorylation, however, was substantially reduced by these inhibitors, as was the TSP-1-induced chemotaxis of these cells. These results suggest that activation of PI 3-K is an early signal induced by TSP-1 and is critical for chemotaxis. Activation of this kinase precedes and may occur upstream from FAK phosphorylation, although the nature of the interaction between these 2 enzymes remains obscure.


Application of the surgical dislocation approach to residual hip deformity secondary to Legg-Calvé-Perthes disease.
Long-term prognosis after Legg-Calvé-Perthes disease (LCPD) depends on the severity of residual hip deformities including a nonspherical femoral head, a short and wide femoral neck, a high riding greater trochanter, and secondary changes in the acetabulum. Hip deformity after healed LCPD may lead to abnormal hip mechanics including femoroacetabular impingement and hip instability secondary to acetabular dysplasia. The surgical dislocation approach has recently been applied to LCPD hip deformity with encouraging short-term results. This approach allows complete dynamic evaluation of the hip joint, identification, and correction of the most common residual deformities. The purpose of this paper is to describe the application of the surgical hip dislocation approach to LCPD deformity and to evaluate the current available literature on the results of this approach to the healed LCPD hip.


Endovascular Tool Segmentation with Multi-lateral Branched Network during Robot-assisted Catheterization.
Robot-assisted catheterization is routinely carried out for intervention of cardiovascular diseases. Meanwhile, the success of endovascular tool navigation depends on visualization and tracking cues available in the robotic platform. Currently, real-time motion analytics are lacking, while poor illumination during fluoroscopy affects existing physics- and learning-based methods used for tool segmentation. A multi-lateral branched network (MLB-Net) is herein proposed for tool segmentation in cardiovascular angiograms. The model has an encoder with multi-lateral separable convolutions and a pyramid decoder. Model training and validation are done on 1320 angiograms obtained during robot-assisted catheterization in rabbit. Model performance, explained with F1-score of 89.01% and mean intersection-over-union of 90.05% on 330 frames, indicates the model's robustness for guidewire segmentation in angiograms. The MLB-Net offers better performance than the state-of-the-art segmentation models such as U-Net, U-Net++ and DeepLabV3. Thus, it could provide basis for endovascular tool tracking and surgical scene analytics during cardiovascular interventions.


Influence of rationality levels on dynamics of heterogeneous Cournot duopolists with quadratic costs.
This paper is intended to investigate the dynamics of heterogeneous Cournot duopoly games, where the first player adopts identical gradient adjustment mechanisms but the second player is endowed with distinct rationality levels. Based on tools of symbolic computations, we introduce a new approach and use it to establish rigorous conditions of the local stability for these models. We analytically investigate the bifurcations and prove that the period-doubling bifurcation is the only possible bifurcation that may occur for all the considered models. The most important finding of our study is regarding the influence of players' rational levels on the stability of heterogeneous duopolistic competition. It is derived that the stability region of the model where the second firm is rational is the smallest, while that of the one where the second firm is boundedly rational is the largest. This fact is counterintuitive and contrasts with relative conclusions in the existing literature. Furthermore, we also provide numerical simulations to demonstrate the emergence of dynamics such as periodic solutions with different orders and strange attractors.


The site of cellulose synthesis. Hormone treatment alters the intracellular location of alkali-insoluble beta-1,4-glucan (cellulose) synthetase activities.
Membrane preparations from growing regions of 8-day old Pisum sativum epicotyls contain multiple beta-1,4-glucan (cellulose) synthetase activities (UDP- or GDP-glucose: beta-1,4-glucan-glucosyl transferase), and the levels of some of these are influenced by treatments with the growth hormone, indoleacetic acid (IAA). When membranes from control epicotyl segments (zero time) are fractionated by isopycnic sedimentation in sucrose density gradients, all of the synthetase activities are associated mainly with Golgi membrane (density 1.55 g/cm3). After decapitation and treatment of epicotyls with IAA, synthetases also appear in a smooth vesicle fraction (density 1.11 g/cm3) which is rich in endoplasmic reticulum (ER) marker enzyme. Major fractions of these synthetases are not recovered in association with plasma membrane or washed cell walls. When [14-C]sucrose is supplied in vivo to segments +/- IAA, radioactive cellulose is deposited only in the wall. Cellulose or cellodextrin precursors do not accumulate in those membranes in which synthetase activities are recovered in vitro. In experiments where tissue slices containing intact cells are supplied with [14C]sugar nucleotide in vitro, alkali-insoluble beta-1,4-glucan is synthesized (presumably outside the protoplast) at rates which greatly exceeded (20-30 times) those obtained using isolated membrane preparations. Progressive disruption of cell structure results in increasing losses of this high activity. These results are consistent with the interpretation that Golgi and ER-associated synthetases are not themselves loci for cellulose synthesis in vivo, but represent enzymes in transit to sites of action at the wall:protoplast omterface. There they operate only if integrity of cellular organization is maintained.


A polyphasic approach leads to seven new species of the cellulose-decomposing genus Sorangium, Sorangium ambruticinum sp. nov., Sorangium arenae sp. nov., Sorangium bulgaricum sp. nov., Sorangium dawidii sp. nov., Sorangium kenyense sp. nov., Sorangium orientale sp. nov. and Sorangium reichenbachii sp. nov.
Seventy-three strains of Sorangium have been isolated from soil samples collected from all over the world. The strains were characterized using a polyphasic approach and phenotypic, genotypic and chemotype analyses clarified their taxonomic relationships. 16S rRNA, xynB1, groEL1, matrix-assisted laser desorption/ioniziation time-of-flight mass spectrometry and API-ZYM analyses were conducted. In addition, from selected representative strains, fatty acids, quinones and phospholipids were analysed. In silico DNA-DNA hybridization and DNA-DNA hybridization against the current type species of Sorangiumcellulosum strain Soce 1871T (DSM 14627T) completed the analyses. Finally, our study revealed seven new species of Sorangium: Sorangium ambruticinum (Soce 176T; DSM 53252T, NCCB 100639T, sequence accession number ERS2488998), Sorangium arenae (Soce 1078T; DSM 105768T, NCCB 100643T, ERS2489002), Sorangium bulgaricum (Soce 321T; DSM 53339T, NCCB 100640T, ERS2488999), Sorangium dawidii (Soce 362T; DSM 105767T, NCCB 100641T, ERS2489000), Sorangium kenyense (Soce 375T; DSM 105741T, NCCB 100642T, ERS2489001), Sorangium orientale (Soce GT47T; DSM 105742T, NCCB 100638T, ERS2501484) and Sorangium reichenbachii (Soce 1828T; DSM 105769T, NCCB 100644T, ERS2489003).


Morphometric study of cervical spinal canal and transverse foramen diameter using computed tomography: Sex difference and relationship to age in Turkish population.
Accurate and detailed spinal canal diameter transverse foraminal morphometry measurements are essential for understanding spinal column-related diseases and surgical planning, especially for transpedicular screw fixation. This is especially because lateral cervical radiographs do not provide accurate measurements. This retrospective study was conducted to measure the dimensions of the transverse foramen sagittal and transverse diameter (TFD), spinal canal diameter, the distance of the spinal canal from the transverse foramina at the C1 to C7 cervical level, and the anteroposterior and TFDs in the Turkish population. A total of 150 patients who underwent cervical spine computed tomographic imaging with a 1:1 gender ratio were enrolled in the study. The sagittal and TFDs of the spinal canal, the distance of the spinal canal from the transverse foramen, and anteroposterior and TFDs in both right and left sides for all cervical levels C1 to C7. Foramina transversal diameters were measured using imaging tools of the imaging software in the radiology unit. The mean age of the study group was 47.99 ± 18.65 (range, 18-80) years. The majority of the distances of the spinal canal from the transverse foramen and antero-posterior (AP) & transverse (T) diameters for cervical vertebrae were significantly higher in male patients (P < .05). However, between age groups, a few measurements were found significantly different. Some of the distances of the spinal canal from the transverse foramen were significantly higher on the right side whereas all AP & T diameters were significantly higher on the left side in both male and female patients (P < .05). Almost all measurements were significantly higher on the left side for younger patients (<65 years) whereas only AP & T diameters were significantly higher on the left side for older patients (>65 years) (P < .05). Computed tomographic imaging is better than conventional radiographs for the preoperative evaluation of the cervical spine and for a better understanding of cervical spine morphometry. Care must be taken during transpedicular screw fixation, especially in female subjects, more so at the C2, C4, and C6 levels due to decreased distance of the spinal canal from the transverse foramina.


Characterization of a Mycobacterium tuberculosis nanocompartment and its potential cargo proteins.
Mycobacterium tuberculosis has evolved various mechanisms by which the bacterium can maintain homeostasis under numerous environmental assaults generated by the host immune response. M. tuberculosis harbors enzymes involved in the oxidative stress response that aid in survival during the production of reactive oxygen species in activated macrophages. Previous studies have shown that a dye-decolorizing peroxidase (DyP) is encapsulated by a bacterial nanocompartment, encapsulin (Enc), whereby packaged DyP interacts with Enc via a unique C-terminal extension. M. tuberculosis also harbors an encapsulin homolog (CFP-29, Mt-Enc), within an operon with M. tuberculosis DyP (Mt-DyP), which contains a C-terminal extension. Together these observations suggest that Mt-DyP interacts with Mt-Enc. Furthermore, it has been suggested that DyPs may function as either a heme-dependent peroxidase or a deferrochelatase. Like Mt-DyP, M. tuberculosis iron storage ferritin protein, Mt-BfrB, and an M. tuberculosis protein involved in folate biosynthesis, 7,8-dihydroneopterin aldolase (Mt-FolB), have C-terminal tails that could also interact with Mt-Enc. For the first time, we show by co-purification and electron microscopy that mycobacteria via Mt-Enc can encapsulate Mt-DyP, Mt-BfrB, and Mt-FolB. Functional studies of free or encapsulated proteins demonstrate that they retain their enzymatic activity within the Mt-Enc nanocompartment. Mt-DyP, Mt-FolB, and Mt-BfrB all have antioxidant properties, suggesting that if these proteins are encapsulated by Mt-Enc, then this nanocage may play a role in the M. tuberculosis oxidative stress response. This report provides initial structural and biochemical clues regarding the molecular mechanisms that utilize compartmentalization by which the mycobacterial cell may aid in detoxification of the local environment to ensure long term survival.


Characterization of a radula opener neuromuscular system in Aplysia.
1. Several lines of evidence suggest that the I7-I10 muscle group contributes to the radula opening phase of behavior in Aplysia; 1) extracellular stimulation of these muscles in reduced preparations causes the halves of the radula to separate, 2) synaptic activity can be recorded from muscles I7-I10 in intact animals when the radula is opening, and 3) motor neurons innervating I7-I10 are activated out of phase with retractor/closer motor neurons during cycles of buccal activity driven by the cerebral-to-buccal interneuron 2 (CBI-2). 2. All of the opener muscles are innervated by the B48 neurons, a bilaterally symmetrical pair of cholinergic motor neurons. B48 neurons produce excitatory junction potentials (EJPs) in opener muscle fibers that summate to produce muscle contractions. Contraction size is determined by the size of depolarization in muscle fibers and/or by action potentials that are triggered by summation of B48-evoked EJPs. 3. In addition to input from B48 neurons, opener muscles also receive excitatory input from the cholinergic multiaction neurons B4/B5. EJPs evoked by stimulation of neurons B4/B5 are 1/10 the size of B48-evoked EJPs. Consequently, changes in muscle tension produced by B4/B5 activity are relatively small. In contrast to B48 neurons, neurons B4/B5 are likely to be active during the closing/retraction phase of behavior. During cycles of buccal activity driven by neuron CBI-2, neurons B4/B5 fire in phase with closer/retractor motor neurons. Thus opener muscles may develop a modest amount of tension during the closing/retraction phase of behavior as a result of synaptic input from neurons B4/B5. 4. Opener muscles may also develop tension during closing/retraction simply by virtue of the fact that they have been stretched. When isolated opener muscles are lengthened, depolarizations are recorded from individual muscle fibers, and muscle tension increases. With sufficient changes in fiber length, action potentials are elicited. These action potentials produce twitchlike muscle contractions that become rhythmic with maintained stretch. Stretch-activated depolarizations are generally first apparent when muscle length is increased by 1 mm. Length changes of 4-5 mm are generally necessary to elicit twitchlike muscle contractions. Changes of 1-2 mm in muscle length are observed when the opener muscle's antagonist, the accessory radula closer, is activated in reduced preparations. 5. Stretch may also modulate B48-induced contractions of the opener muscles. When muscle length is increased, B48-elicited contractions of the I7 muscle are larger. These increases in contraction amplitude are accompanied by decreases in contraction latency. 6. We conclude that muscles I7-I10 contract vigorously in response to strong excitatory input from neuron B48 and contribute to radula opening. Stretch may potentiate this activity. Thus, if radula closer muscles contract vigorously and pull on the opener muscles, the opener muscles will respond by contracting more vigorously themselves. This may be a mechanism for maintaining amplitude relationships between antagonistic muscles. Additionally, it is likely that the opener muscles will develop at least a modest amount of tension during closure/retraction of the radula. Part of this activation may derive from the weak excitatory input that the muscles receive from neurons B4/B5. Another part may derive from the stretch. One function of this co-contraction may be to act as a brake on closure, bringing this phase of feeding behavior to a smooth halt.


Facilitative effects of the ampakine CX516 on short-term memory in rats: enhancement of delayed-nonmatch-to-sample performance.
Ampakines are a family of drugs that selectively increase AMPA receptor-gated currents and improve performance on several behavioral tasks. This report describes evidence that ampakines cause a cumulative enhancement of performance in a spatial short-term memory task (Deadwyler et al., 1996). Two groups of rats were trained on a spatial variant of the delayed-nonmatch-to-sample (DNMS) paradigm. One group (n = 12) received the ampakine CX516 (Cortex Pharmaceuticals) alternated with vehicle for 17 consecutive days and then only vehicle for an additional 7 d. The second group (n = 6) received only vehicle injections over the same number of days. CX516 improved performance within sessions, particularly on trials with delays of 6-35 sec. In 9 of 12 rats, the positive effect of the drug was also present on nondrug days between CX516 administration and after cessation of CX516 injections. The animals that received only vehicle injections showed no improvement in DNMS performance over the entire 32 d of testing. Three of the 12 animals given CX516 did not exhibit "carryover" effects of the drug to the intervening (vehicle only) test sessions, but nonetheless exhibited superior performance during the first half of the session on days in which the ampakine was administered. Evaluation of errors suggests that the ampakine eliminated the necessity for a shift in response strategy that produced proactive interference on the following trial. Hippocampal involvement in these ampakine effects is discussed as a prelude to the second article in the series (Hampson et al., 1998).


Oxidative stress effect on the activation of hepatic stellate cells.
Collagen is the most excessive extracellular matrix protein in hepatic fibrosis. Activated, but not quiescent, hepatic stellate cells (HSCs) have a high level of collagen and a smooth muscle actin (alpha SMA) expression. HSCs play a key role in the pathogenesis of hepatic fibrosis. We analyzed a mechanism leading to HSC activation by evaluating the role of oxidative stress and the expression of NFkB. In vitro study HSCs were proliferated (PCNA:2% vs 68%) and activated (alpha SMA: 5% vs 78%) by ascorbate/FeSO4, and HSCs activated by type I collagen were blocked (PCNA: 97% vs 4%, a SMA: 86% vs 9%) by a-tocopherol. In vivo study means of a SMA positive cells in liver at 400 x HPF were 48.3+/-5.2 and 15.2+/-1.8 and [3H]thymidine uptake of HSC was 529.2+/-284.8 cpm and 223.0+/-86.3 cpm in control and a-tocopherol treated group respectively at 32 hours after CCl4 injection. Nuclear extracts from activated, but not from quiescent, HSCs formed a complex with the NFkB cognate oligonucleotidesand alpha-tocopherol inhibited this bindings. This study indicates that oxidative stress plays an essential role through the induction of NFkB on HSC activation.


Magnetite Nanoparticles: Synthesis and Applications in Optics and Nanophotonics.
Magnetite nanoparticles with different surface coverages are of great interest for many applications due to their intrinsic magnetic properties, nanometer size, and definite surface morphology. Magnetite nanoparticles are widely used for different medical-biological applications while their usage in optics is not as widespread. In recent years, nanomagnetite suspensions, so-called magnetic ferrofluids, are applied in optics due to their magneto-optical properties. This review gives an overview of nanomagnetite synthesis and its properties. In addition, the preparation and application of magnetic nanofluids in optics, nanophotonics, and magnetic imaging are described.


Deficiency of serum "pregnancy-associated" alpha 2-glycoprotein alpha 2-PAG): association with disease.
The serum concentrations of "pregnancy-associated" alpha 2-glycoprotein (alpha 2-PAG) were measured in 129 healthy women and 141 healthy men to establish a normal range, using a sensitive enzyme linked immunosorbent assay. In the normal population 2.8% of men and 5.4% of women had low serum alpha 2-PAG concentrations. Low concentrations occur, however, much more commonly in patients, particularly male patients, with certain diseases, including dermatitis herpetiformis (three of 12 or 25%) and urticaria (two of five or 40%). One female patient with absolute deficiency was also identified. In view of the recently confirmed association of alpha 2-PAG with IgA and the fact that alpha 2-PAG seems to have immunosuppressive properties, it seems likely that deficiency of alpha 2-PAG could result in the subject becoming sensitised to various dietary antigens. Interestingly, none of the 24 patients with IgA deficiency showed concomitant deficiency of alpha 2-PAG.


Workplace stress in nursing: a literature review.
Stress perception is highly subjective, and so the complexity of nursing practice may result in variation between nurses in their identification of sources of stress, especially when the workplace and roles of nurses are changing, as is currently occurring in the United Kingdom health service. This could have implications for measures being introduced to address problems of stress in nursing. To identify nurses' perceptions of workplace stress, consider the potential effectiveness of initiatives to reduce distress, and identify directions for future research. A literature search from January 1985 to April 2003 was conducted using the key words nursing, stress, distress, stress management, job satisfaction, staff turnover and coping to identify research on sources of stress in adult and child care nursing. Recent (post-1997) United Kingdom Department of Health documents and literature about the views of practitioners was also consulted. Workload, leadership/management style, professional conflict and emotional cost of caring have been the main sources of distress for nurses for many years, but there is disagreement as to the magnitude of their impact. Lack of reward and shiftworking may also now be displacing some of the other issues in order of ranking. Organizational interventions are targeted at most but not all of these sources, and their effectiveness is likely to be limited, at least in the short to medium term. Individuals must be supported better, but this is hindered by lack of understanding of how sources of stress vary between different practice areas, lack of predictive power of assessment tools, and a lack of understanding of how personal and workplace factors interact. Stress intervention measures should focus on stress prevention for individuals as well as tackling organizational issues. Achieving this will require further comparative studies, and new tools to evaluate the intensity of individual distress.


Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/gammac(null) mice: suppression by an inhibitor against NF-kappaB.
We established a novel experimental model for human T-cell leukemia virus type 1 (HTLV-1)-induced tumor using NOD-SCID/gammac(null) (NOG) mice. This model is very useful for investigating the mechanism of tumorigenesis and malignant cell growth of adult T-cell leukemia (ATL)/lymphoma, which still remains unclear. Nine HTLV-1-infected cell lines were inoculated subcutaneously in the postauricular region of NOG mice. As early as 2 to 3 weeks after inoculation, seven cell lines produced a visible tumor while two transformed cell lines failed to do so. Five of seven lines produced a progressively growing large tumor with leukemic infiltration of the cells in various organs that eventually killed the animals. Leukemic cell lines formed soft tumors, whereas some transformed cell lines developed into hemorrhagic hard tumors in NOG mice. One of the leukemic cell lines, ED-40515(-), was unable to produce visible tumors in NOD-SCID mice with a common gamma-chain after 2 weeks. In vivo NF-kappaB DNA binding activity of the ED-40515(-) cell line was higher and the NF-kappaB components were changed compared to cells in vitro. Bay 11-7082, a specific and effective NF-kappaB inhibitor, prevented tumor growth at the sites of the primary region and leukemic infiltration in various organs of NOG mice. This in vivo model of ATL could provide a novel system for use in clarifying the mechanism of growth of HTLV-1-infected cells as well as for the development of new drugs against ATL.


Contrasting outcomes of species- and community-level analyses of the temporal consistency of functional composition.
Multiple anthropogenic drivers affect every natural community, and there is broad interest in using functional traits to understand and predict the consequences for future biodiversity. There is, however, no consensus regarding the choice of analytical methods. We contrast species- and community-level analyses of change in the functional composition for four traits related to drought tolerance using three decades of repeat censuses of trees in the 50-ha Forest Dynamics Plot on Barro Colorado Island, Panama. Community trait distributions shifted significantly through time, which may indicate a shift toward more drought tolerant species. However, at the species level, changes in abundance were unrelated to trait values. To reconcile these seemingly contrasting results, we evaluated species-specific contributions to the directional shifts observed at the community level. Abundance changes of just one to six of 312 species were responsible for the community-level shifts observed for each trait. Our results demonstrate that directional changes in community-level functional composition can result from idiosyncratic change in a few species rather than widespread community-wide changes associated with functional traits. Future analyses of directional change in natural communities should combine community-, species-, and possibly individual-level analyses to uncover relationships with function that can improve understanding and enable prediction.


A quality improvement project to tackle under-reporting of hazards by doctors by using an anonymous telephone hotline.
An anonymous hazard reporting hotline was established for doctors to use on two general medical wards at Weston General Hospital (WGH) in North Somerset in England during an eight day period in July/August 2014. Doctors were encouraged to report hazards and near misses or just start a conversation about a concern. The existing computer based significant event system remained alongside the hotline and was to be used where actual harm had come to a patient. A team of consultants and quality improvement administrators monitored the hotline on a daily basis, categorized the level of risk being reported and ensured, where possible, that action was taken to address the doctors' concerns. The hotline increased reporting rates from two per month to 25 in eight days. The system identified 13 amber (medium risk) and five red (high risk) hazards which would otherwise not have been known about. This author believes these five high risk reports alone make the case for a new, quicker, easier, and anonymous reporting system for doctors at WGH urgent and irrefutable.


Phase II study of asparagine-glycine-arginine-human tumor necrosis factor alpha, a selective vascular targeting agent, in previously treated patients with malignant pleural mesothelioma.
NGR-hTNF consists of human tumor necrosis factor alpha (hTNF-alpha) fused to the tumor-homing peptide asparagine-glycine-arginine (NGR) able to selectively bind an aminopeptidase N isoform overexpressed on tumor blood vessels. Hypervascularity is a prominent and poor-prognosis feature of malignant pleural mesothelioma (MPM). Currently, there are no standard options for patients with MPM who are failing a front-line pemetrexed-based regimen. We explored safety and efficacy of NGR-hTNF in this setting. Eligible patients had radiologically documented tumor progression and performance status < or = 2. Primary study aim was progression-free survival (PFS). NGR-hTNF 0.8 microg/m(2) was given intravenously every 3 weeks. A subsequent cohort of patients received 0.8 microg/m(2) on a weekly basis. In the triweekly cohort (n = 43), only one grade 3 drug-related toxicity was noted, and the most common grades 1 to 2 were short-lived chills (71%). The median PFS was 2.8 months (95% CI, 2.3 to 3.3 months). Nineteen patients (44%) had disease control (one had partial response, and 18 had stable diseases) and experienced a median progression-free time of 4.4 months. In the weekly cohort (n = 14), there was no higher toxicity, and median PFS was 3.0 months (95% CI, 1.9 to 4.1 months). Seven patients (50%) had disease control (all stable diseases) and had a median progression-free interval of 9.1 months. In the overall study population (N = 57), median PFS was 2.8 months. Median progression-free time was 4.7 months in twenty-six patients (46%) who achieved disease control. Median survival was 12.1 months. The tolerability and disease control of NGR-hTNF 0.8 microg/m(2) weekly warrant additional evaluation in patients with advanced MPM.


Disorders of diminished motivation.
Disorders of diminished motivation occur frequently in individuals with traumatic brain injury. Motivation is an ever-present, essential determinant of behavior and adaptation. The major syndromes of diminished motivation are apathy, abulia, and akinetic mutism. Depending on their etiology, disorders of diminished motivation may be a primary clinical disturbance, a symptom of another disorder, or a coexisting second disorder. This article presents a biopsychosocial approach to the assessment and management of motivational impairments in patients with traumatic brain injury. The recognition and differential diagnosis of disorders of diminished motivation, as well as the mechanism and clinical pathogenesis, are discussed.


Soybean peroxidase-catalyzed removal of an aromatic thiol, 2-mercaptobenzothiazole, from water.
This paper demonstrates, for the first time, the capability of soybean peroxidase (SBP), an enzyme, for catalyzing the removal of an aromatic thiol, 2-mercaptobenzothiazole (MBT), from aqueous solution. The optimum pH for enzymatic conversion of MBT in aqueous buffer was found to be in the range 6.0 to 9.0. The optimum hydrogen peroxide (H2O2): MBT stoichiometry was 0.6. In terms of standard units (U) of catalytic activity, the minimum SBP concentration required for 95% conversion of 1.0 mM MBT in 3 hours was found to be 0.9 U/mL. The presence of polyethylene glycol at 50 mg/L can reduce the enzyme concentration required for the same conversion by 3-fold. It is proposed that these findings should be the basis for viable and cost-effective treatment of MBT in industrial wastewater and/or process water.