bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey
Authors: Ballerini Andrea , Boccalon Roberto M , Boncompagni Giancarlo , Casacchia Massimo , Margari Francesco , Minervini Lina , Righi Roberto , Russo Federico , Salteri Andrea , Frediani Sonia , Rossi Andrea , Scatigna Marco ,   the PERSEO study group
Published: November 2007

Abstract

Background
The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications.

Methods
A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period.

Results
Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay.

Conclusion
Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.
Oculocutaneous albinism
Authors: Grønskov Karen , Ek Jakob , Brondum-Nielsen Karen 
Published: November 2007

Abstract
Oculocutaneous albinism (OCA) is a group of inherited disorders of melanin biosynthesis characterized by a generalized reduction in pigmentation of hair, skin and eyes. The prevalence of all forms of albinism varies considerably worldwide and has been estimated at approximately 1/17,000, suggesting that about 1 in 70 people carry a gene for OCA. The clinical spectrum of OCA ranges, with OCA1A being the most severe type with a complete lack of melanin production throughout life, while the milder forms OCA1B, OCA2, OCA3 and OCA4 show some pigment accumulation over time. Clinical manifestations include various degrees of congenital nystagmus, iris hypopigmentation and translucency, reduced pigmentation of the retinal pigment epithelium, foveal hypoplasia, reduced visual acuity usually (20/60 to 20/400) and refractive errors, color vision impairment and prominent photophobia. Misrouting of the optic nerves is a characteristic finding, resulting in strabismus and reduced stereoscopic vision. The degree of skin and hair hypopigmentation varies with the type of OCA. The incidence of skin cancer may be increased. All four types of OCA are inherited as autosomal recessive disorders. At least four genes are responsible for the different types of the disease (TYR, OCA2, TYRP1 and MATP). Diagnosis is based on clinical findings of hypopigmentation of the skin and hair, in addition to the characteristic ocular symptoms. Due to the clinical overlap between the OCA forms, molecular diagnosis is necessary to establish the gene defect and OCA subtype. Molecular genetic testing of TYR and OCA2 is available on a clinical basis, while, at present, analysis of TYRP1 and MATP is on research basis only. Differential diagnosis includes ocular albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome, and Waardenburg syndrome type II. Carrier detection and prenatal diagnosis are possible when the disease causing mutations have been identified in the family. Glasses (possibly bifocals) and dark glasses or photocromic lenses may offer sufficient help for reduced visual activity and photophobia. Correction of strabismus and nystagmus is necessary and sunscreens are recommended. Regular skin checks for early detection of skin cancer should be offered. Persons with OCA have normal lifespan, development, intelligence and fertility.
Angiopoietin-mediated endothelial P-selectin translocation: cell signaling mechanisms
Authors: Maliba Ricardo , Brkovic Alexandre , Neagoe Paul-Éduard , Villeneuve Louis R , Sirois Martin G 
Published: November 2007

AbstractRecently identified, angiopoietin-1 (Ang1) and -2 (Ang2) bind to the tyrosine kinase receptor Tie2 and contribute to orchestrate blood vessel formation during angiogenesis. Ang1 mediates vessel maturation and integrity by favoring the recruitment of pericytes and smooth muscle cells. Ang2, initially identified as a Tie2 antagonist, may under certain circumstances, induce Tie2 phosphorylation and biological activities. As inflammation exists in a mutually dependent association with angiogenesis, we sought to determine if Ang1 and/or Ang2 could modulate proinflammatory activities, namely P-selectin translocation, in bovine aortic endothelial cells (EC) and dissect the mechanisms implicated. P-selectin, an adhesion molecule found in the Weibel-Palade bodies of EC, is translocated rapidly to the cell surface upon EC activation during inflammatory processes. Herein, we report that Ang1 and Ang2 (1 nM) are capable of mediating a rapid Tie2 phosphorylation as well as a rapid and transient endothelial P-selectin translocation maximal within 7.5 min (125% and 100% increase, respectively, over control values). In addition, we demonstrate for the first time that angiopoietin-mediated endothelial P-selectin translocation is calcium-dependent and regulated through phospholipase C-γ activation.
Alemtuzumab Compared With Chlorambucil As First-Line Therapy for Chronic Lymphocytic Leukemia
Authors: Hillmen Peter , Skotnicki Aleksander B. , Robak Tadeusz , Jaksic Branimir , Dmoszynska Anna , Wu Jingyang , Sirard Cynthia , Mayer Jiri 
Published: November 2007

Purpose We conducted a randomized trial to evaluate the efficacy and safety of intravenous alemtuzumab compared with chlorambucil in first-line treatment of chronic lymphocytic leukemia (CLL). Patients and Methods Patients received alemtuzumab (30 mg three times per week, for up to 12 weeks) or chlorambucil (40 mg/m2 every 28 days, for up to 12 months). The primary end point was progression-free survival (PFS). Secondary end points included overall response rate (ORR), complete response (CR), time to alternative therapy, safety, and overall survival. Results We randomly assigned 297 patients, 149 to alemtuzumab and 148 to chlorambucil. Alemtuzumab had superior PFS, with a 42% reduction in risk of progression or death (hazard ratio [HR] = 0.58; P = .0001), and a median time to alternative treatment of 23.3 versus 14.7 months for chlorambucil (HR = 0.54; P = .0001). The ORR was 83% with alemtuzumab (24% CR) versus 55% with chlorambucil (2% CR); differences in ORR and CR were highly statistically significant (P < .0001). Elimination of minimal residual disease occurred in 11 of 36 complete responders to alemtuzumab versus none to chlorambucil. Adverse events profiles were similar, except for more infusion-related and cytomegalovirus (CMV) events with alemtuzumab and more nausea and vomiting with chlorambucil. CMV events had no apparent impact on efficacy. Conclusion As first-line treatment for patients with CLL, alemtuzumab demonstrated significantly improved PFS, time to alternative treatment, ORR and CR, and minimal residual disease–negative remissions compared with chlorambucil, with predictable and manageable toxicity.
Pituitary-Specific Knockout of the Carney Complex Gene Prkar1a Leads to Pituitary Tumorigenesis
Authors: Yin Zhirong , Williams-Simons Lisa , Parlow A. F. , Asa Sylvia , Lawrence S. Lawrence S. 
Published: November 2007

AbstractCarney complex (CNC) is an inherited neoplasia syndrome characterized by spotty skin pigmentation, myxomas, endocrine tumors, and schwannomas. Among the endocrine tumors that comprise the syndrome, GH-producing pituitary tumors are seen in approximately 10% of patients, although biochemical abnormalities of the GH axis are much more common. To explore the role of loss of the CNC gene PRKAR1A on pituitary tumorigenesis, we produced a tissue-specific knockout (KO) of this gene in the mouse. For these studies, we generated a mouse line expressing the cre recombinase in pituitary cells using the rat GHRH receptor promoter. These mice were then crossed with Prkar1a conditional null animals to produce tissue-specific KOs. Although prolactinomas were observed in KO and control mice, the KO mice exhibited a significantly increased frequency of pituitary tumors compared with wild-type or conventional Prkar1a+/− mice. Characterization of the tumors demonstrated they were composed of cells of the Pit1 lineage that stained for GH, prolactin, and TSH. At the biochemical level, levels of GH in the serum of KO animals were markedly elevated compared with controls, regardless of the presence of a frank tumor. These data indicate that complete loss of Prkar1a is sufficient to allow the formation of pituitary tumors and abnormalities of the GH axis, in close analogy to human patients with CNC.
Combinatorial Roles of Protein Kinase A, Ets2, and 3′,5′-Cyclic-Adenosine Monophosphate Response Element-Binding Protein-Binding Protein/p300 in the Transcriptional Control of Interferon-τ Expression in a Trophoblast Cell Line
Authors: Das Padmalaya , Ezashi Toshihiko , Gupta Rangan , Roberts R. Michael 
Published: November 2007

AbstractIn ruminants, conceptus interferon-τ (IFNT) production is necessary for maintenance of pregnancy. We examined the role of protein kinase A (PKA) in regulating IFNT expression through the activation of Ets2 in JAr choriocarcinoma cells. Although overexpression of the catalytic subunit of PKA or the addition of 8-bromo-cAMP had little ability to up-regulate boIFNT1 reporter constructs on their own, coexpression with Ets2 led to a large increase in gene expression. Progressive truncation of reporter constructs indicated that the site of PKA/Ets2 responsiveness lay in a region of the promoter between −126 and −67, which lacks a cAMP response element but contains the functional Ets2-binding site and an activator protein 1 (AP1) site. Specific mutation of the former reduced the PKA/Ets2 effects by more than 98%, whereas mutation of an AP1-binding site adjacent to the Ets2 site or pharmacological inhibition of MAPK kinase 2 led to a doubling of the combined Ets2/PKA effects, suggesting there is antagonism between the Ras/MAPK pathway and the PKA signal transduction pathway. Although Ets2 is not a substrate for PKA, lowering the effective concentrations of the coactivators, cAMP response element-binding protein-binding protein (CBP)/p300, known PKA targets, reduced the ability of PKA to synergize with Ets2, suggesting that PKA effects on IFNT regulation might be mediated through CBP/p300 coactivation, particularly as CBP and Ets2 occupy the proximal promoter region of IFNT in bovine trophoblast CT-1 cells. The up-regulation of IFNT in the elongating bovine conceptus is likely due to the combinatorial effects of PKA, Ets2, and CBP/p300 and triggered via growth factors released from maternal endometrium.
Interplay of Nuclear Factor-κB and B-myb in the Negative Regulation of Androgen Receptor Expression by Tumor Necrosis Factor α
Authors: Ko Soyoung , Shi Liheng , Kim Soyoung , Song Chung S. , Chatterjee Bandana 
Published: November 2007

Abstract
Increased androgen receptor (AR) levels are associated with prostate cancer progression to androgen independence and therapy resistance. Evidence has suggested that chronic inflammation is closely linked to various cancers including prostate cancer. Herein we show that the proinflammatory cytokine TNFα negatively regulates AR mRNA and protein expression and reduces androgen sensitivity in androgen-dependent LNCaP human prostate cancer cells. Decreased AR expression results from transcription repression involving essential in cis interaction of nuclear factor-κB (NF-κB) with the B-myb transcription factor at a composite genomic element in the 5′-untranslated region of AR. The negative regulation was abrogated when NF-κB activity was inhibited by a superrepressor of the inhibitory κB protein. In contrast, androgen-independent C4-2 (LNCaP-derived) cells fail to show AR down-regulation by TNFα, despite expression of B-myb and TNFα-induced NF-κB activity similar to that in LNCaP cells. The negatively regulated AR gene chromatin region showed TNFα-dependent enrichment of B-myb and the NF-κB proteins p65 and p50. In parallel, the histone deacetylase 1, corepressor silencing mediator of retinoid and thyroid hormone receptor and the corepressor-associated scaffold protein mSin3A were recruited to the inhibitory site. In C4-2 cells, neither NF-κB and B-myb, nor any of the corepressor components, were detected at the negative site in response to TNFα. Apoptosis was induced in TNFα-treated LNCaP cells, likely in part due to the down-regulation of AR. The androgen-independent, AR-expressing C4-2 and C4-2B (derived from C4-2) cells were resistant to TNFα-induced apoptosis. The results linking androgen dependence to the NF-κB and AR pathways may be insightful in identifying novel treatment targets for prostate cancer.
Prolactin Signaling through the Short Form of Its Receptor Represses Forkhead Transcription Factor FOXO3 and Its Target Gene Galt Causing a Severe Ovarian Defect
Authors: Halperin Julia , Devi Sangeeta Y. , Elizur Shai , Stocco Carlos , Shehu Aurora , Rebourcet Diane , Unterman Terry G. , Leslie Nancy D. , Le Jamie , Binart Nadine , Gibori Geula 
Published: November 2007

Abstract
Prolactin (PRL) is a hormone with over 300 biological activities. Although the signaling pathway downstream of the long form of its receptor (RL) has been well characterized, little is known about PRL actions upon activation of the short form (RS). Here, we show that mice expressing only RS exhibit an ovarian phenotype of accelerated follicular recruitment followed by massive follicular death leading to premature ovarian failure. Consequently, RS-expressing ovaries of young adults are depleted of functional follicles and formed mostly by interstitium. We also show that activation of RS represses the expression of the transcription factor Forkhead box O3 (FOXO3) and that of the enzyme galactose-1-phosphate uridyltransferase (Galt), two proteins known to be essential for normal follicular development. Our finding that FOXO3 regulates the expression of Galt and enhances its transcriptional activity indicates that it is the repression of FOXO3 by PRL acting through RS that prevents Galt expression in the ovary and causes follicular death. Coexpression of RL with RS prevents PRL inhibition of Galt, and the ovarian defect is no longer seen in RS transgenic mice that coexpress RL, suggesting that RL prevents RS-induced ovarian impairment. In summary, we show that PRL signals through RS and causes, in the absence of RL, a severe ovarian pathology by repressing the expression of FOXO3 and that of its target gene Galt. We also provide evidence of a link between the premature ovarian failure seen in mice expressing RS and in mice with FOXO3 gene deletion as well as in human with Galt mutation.
Flight performance in night-flying sweat bees suffers at low light levels
Authors: Theobald Jamie Carroll , Coates Melissa M. , Wcislo William T. , Warrant Eric J. 
Published: November 2007

SUMMARYThe sweat bee Megalopta (Hymenoptera: Halictidae), unlike most bees, flies in extremely dim light. And although nocturnal insects are often equipped with superposition eyes, which greatly enhance light capture, Megalopta performs visually guided flight with apposition eyes. We examined how light limits Megalopta's flight behavior by measuring flight times and corresponding light levels and comparing them with flight trajectories upon return to the nest. We found the average time to land increased in dim light, an effect due not to slow approaches, but to circuitous approaches. Some landings, however, were quite fast even in the dark. To explain this, we examined the flight trajectories and found that in dim light, landings became increasingly error prone and erratic, consistent with repeated landing attempts. These data agree well with the premise that Megalopta uses visual summation, sacrificing acuity in order to see and fly at the very dimmest light intensities that its visual system allows.
An antidiuretic peptide (Tenmo-ADFb) with kinin-like diuretic activity on Malpighian tubules of the house cricket, Acheta domesticus (L.)
Authors: Coast Geoffrey M. , Nachman Ronald J. , Schooley David A. 
Published: November 2007

SUMMARY
Acheta domesticus is reported to have an antidiuretic hormone that reduces Malpighian tubule secretion. Identified peptides known to work in this way (Tenmo-ADFa and ADFb, and Manse-CAP2b) were tested as candidates for the unidentified hormone, along with their second messenger,cyclic GMP. Only Tenmo-ADFb was active, but was diuretic, as was 8-bromo cyclic GMP. The activity of Tenmo-ADFb is comparable to that of the cricket kinin neuropeptide, Achdo-KII, but it is much less potent. Its activity was unaffected by deleting either the six N-terminal residues or the C-terminal phenylalanine.
At high concentrations, tubule secretion is doubled by Tenmo-ADFb and Achdo-KII, but their actions are non-additive, suggesting they have a similar mode of action. Both stimulate a non-selective KCl and NaCl diuresis, which is consistent with the opening of a transepithelial Cl–conductance. In support of this, the diuretic response to Tenmo-ADFb and Achdo-KII is prevented by a ten-fold reduction in bathing fluid chloride concentration, and both peptides cause the lumen-positive transepithelial voltage to collapse. The Cl– conductance pathway appears likely to be transcellular, because the Cl– channel blocker DPC reduces both basal and peptide-stimulated rates of secretion. The effects of 8-bromo cyclic GMP on transepithelial voltage and composition of the secreted fluid are markedly different from those of Tenmo-ADFb.
This is the first report of the antidiuretic factor Tenmo-ADFb stimulating tubule secretion. Although the actions of Tenmo-ADFb are indistinguishable from those of Achdo-KII, it is unlikely to act at a kinin receptor, because the core sequence (residues 7–12) lacks the Phe and Trp residues that are critical for kinin activity.
Temperature and food mediate long-term thermotactic behavioral plasticity by association-independent mechanisms in C. elegans
Authors: Chi Cynthia A. , Clark Damon A. , Lee Stella , Biron David , Luo Linjiao , Gabel Christopher V. , Brown Jeffrey , Sengupta Piali , Samuel Aravinthan D. T. 
Published: November 2007

SUMMARY
Thermotactic behavior in the nematode Caenorhabditis elegansexhibits long-term plasticity. On a spatial thermal gradient, C. elegans tracks isotherms near a remembered set-point(TS) corresponding to its previous cultivation temperature. When navigating at temperatures above its set-point(T&gt;TS), C. elegans crawls down spatial thermal gradients towards the TS in what is called cryophilic movement. The TS retains plasticity in the adult stage and is reset by ∼4 h of sustained exposure to a new temperature. Long-term plasticity in C. elegans thermotactic behavior has been proposed to represent an associative learning of specific temperatures conditioned in the presence or absence of bacterial food. Here,we use quantitative behavioral assays to define the temperature and food-dependent determinants of long-term plasticity in the different modes of thermotactic behavior. Under our experimental conditions, we find that starvation at a specific temperature neither disrupts TSresetting toward the starvation temperature nor induces learned avoidance of the starvation temperature. We find that prolonged starvation suppresses the cryophilic mode of thermotactic behavior. The hen-1 and tax-6 genes have been reported to affect associative learning between temperature and food-dependent cues. Under our experimental conditions,mutation in the hen-1 gene, which encodes a secreted protein with an LDL receptor motif, does not significantly affect thermotactic behavior or long-term plasticity. Mutation in the tax-6 calcineurin gene abolishes thermotactic behavior altogether. In summary, we do not find evidence that long-term plasticity requires association between temperature and the presence or absence of bacterial food.
Morphology and kinematics of feeding in hagfish: possible functional advantages of jaws
Authors: Clark Andrew J. , Summers Adam P. 
Published: November 2007

SUMMARYAs in gnathostomes, the hagfish feeding apparatus includes skeletal, dental and muscular components. In the present study, we examined feeding morphology and kinematics in two hagfish species, Eptatretus stoutii and Myxine glutinosa, representing the two major hagfish lineages. E. stoutii have larger dental plates, larger basal plates, and stronger clavatus muscles (the major dental plate retractor) than M. glutinosa. Despite morphological differences, kinematic profiles are similar in E. stoutii and M. glutinosa. When protracted, the dental plate unfolds and exposes keratinous teeth, which are then embedded in the prey. Once food is grasped, the dental plate is retracted into the mouth. During retraction, the clavatus muscle can generate up to 16 N of force, which exceeds the bite force of some gnathostomes of similar size. In addition to producing high forces with the feeding muscles, hagfish can evert their dental plates to 180°, exceeding the gape angles attained by virtually all gnathostomes, suggesting vertebrate jaws are not the prerequisites for muscle force generation and wide gapes. We propose that dental plate protraction and retraction can be modeled as a fixed pulley that lacks the speed amplification occurring in gnathostome jaws. Hagfish gape cycle times are approximately 1 s,and are longer than those of gnathostomes, suggesting that a functional advantage of jaws is the speed that allows gnathostomes to exploit elusive prey.