Efficacy and safety of intralesional corticosteroid application for hemangiomas.
There are different modalities for management of infantile hemangiomas (IHs). In this report, our aim is to evaluate whether intralesional corticosteroid treatment is associated with systemic side effects and whether this is an effective treatment modality for IH. Six children treated with intralesional corticosteroids for problematic hemangiomas were included in the study. Clinical characteristics, response to treatment, weight, height, blood pressure, morning serum cortisol, and adrenocorticotropic hormone levels were recorded. Each child received intralesional triamcinolone at a dose of 2 mg/kg for 2-5 injections at monthly intervals. Subjects were followed for 1 year. All patients had adrenal suppression following the second or third triamcinolone injections. Five patients demonstrated partial response and one demonstrated no response. Intralesional steroid injection may effectively induce the resolution of hemangiomas, but all the patients in our group had adrenal suppression after treatment. The use of intralesional steroid therapy is not a superior treatment option for hemangiomas. It also has side effects comparable to systemic steroids.


Pedunculopontine and laterodorsal tegmental nuclei contain distinct populations of cholinergic, glutamatergic and GABAergic neurons in the rat.
The pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) provide cholinergic afferents to several brain areas. This cholinergic complex has been suggested to play a role in sleep, waking, motor function, learning and reward. To have a better understanding of the neurochemical organization of the PPTg/LDTg we characterized the phenotype of PPTg/LDTg neurons by determining in these cells the expression of transcripts encoding choline acetyltransferase (ChAT), glutamic acid decarboxylase (GAD) or the vesicular glutamate transporters (vGluT1, vGluT2 and vGluT3). Within the PPTg/LDTg complex we found neurons expressing ChAT, vGluT2 or GAD transcripts, these neuronal phenotypes were intermingled, but not homogeneously distributed within the PPTg or LDTg. Previous studies suggested the presence of either glutamate or gamma-aminobutyric acid (GABA) immunolabeling in a large number of PPTg/LDTg cholinergic neurons, leading to the widespread notion that PPTg/LDTg cholinergic neurons co-release acetylcholine together with either glutamate or GABA. To assess the glutamatergic or GABAergic nature of the PPTg/LDTg cholinergic neurons, we combined in situ hybridization (to detect vGluT2 or GAD transcripts) and immunohistochemistry (to detect ChAT), and found that over 95% of all PPTg/LDTg cholinergic neurons lack transcripts encoding either vGluT2 mRNA or GAD mRNA. As the vast majority of PPTg/LDTg cholinergic neurons lack transcripts encoding essential proteins for the vesicular transport of glutamate or for the synthesis of GABA, co-release of acetylcholine with either glutamate or GABA is unlikely to be a major factor in the interactions between acetylcholine, glutamate and GABA at the postsynaptic site.


TCR repertoire, clonal dominance, and pulmonary trafficking of mycobacterium-specific CD4+ and CD8+ T effector cells in immunity against tuberculosis.
Clonal responses of Mycobacterium tuberculosis-specific CD4(+) or CD8(+) T effector cells producing antituberculosis cytokine IFN-γ in the context of immune protection against tuberculosis remain poorly characterized in humans. Utilizing decade-long TCR expertise, we previously developed a useful method to isolate clonotypic TCR sequences from Ag-specific IFN-γ-producing T cells and to specifically measure clonotypic TCR frequencies in the T cell pool. In this study, we investigated TCR Vβ repertoires/CDR3 usage, clonal expansion or dominance, and pulmonary trafficking or accumulation for purified protein deritative (PPD)-specific T effector cells producing IFN-γ during bacillus Calmette-Guérin (BCG) vaccination and subsequent M. tuberculosis challenge of macaques. We found that while PPD-specific CD4(+) and CD8(+) T effector clones employed diverse TCR Vβ repertoires, 30-33% of IFN-γ(+)CD4(+) T cell clones from three M. tuberculosis-infected macaques expressed TCR bearing a conserved residue leucine in CDR3. Many Ag-specific IFN-γ(+) CD4(+) and few CD8(+) T effector cells emerged as dominant clones during mycobacterial infections and underwent major recall expansion after pulmonary M. tuberculosis infection of BCG-vaccinated macaques. PPD-specific T cell clones readily trafficked to the airway or lung after BCG vaccination or M. tuberculosis infection, and some of them continuously accumulated in lungs during M. tuberculosis infection even after they became undetectable in the circulation. Importantly, remarkable recall expansion and pulmonary accumulation of T effector cells coincided with BCG-induced protection against tuberculosis. Thus, rapid clonal expansion and pulmonary accumulation of Ag-specific T effector cells appear to be one of the immune mechanisms underlying immunity against tuberculosis.


Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury.
Thrombin and other proteinases exert vascular effects by activating the proteinase-activated receptors (PARs). The expression of PARs has been shown to be upregulated after balloon injury and in human arteriosclerosis. However, the relationship between the receptor upregulation and the alteration of vasomotor function remains to be elucidated. We herein demonstrated that the contractile responses to the PAR-1 and PAR-2 agonist were markedly enhanced in the rabbit femoral arteries after balloon injury. Neointimal thickening was established 4 wk after the injury. No histological change was observed in the sham operation, where the saphenous artery was ligated without any balloon injury. The contractile response to K(+) depolarization was significantly attenuated 1 wk after the injury and then partly recovered after 4 wk. Thrombin, PAR-1-activating peptide, trypsin, and PAR-2-activating peptide induced no significant contraction in the control. All these stimulants induced enhanced responses 1 wk after balloon injury. Such enhanced responses were seen 4 wk after the injury, except for thrombin. There was no change in the Ca(2+) sensitivity of the contractile apparatus as evaluated in the permeabilized preparations. PAR-1-activating peptide (100 mumol/l), but no other stimulants, induced an enhanced contraction in the sham operation. The expression of PAR-1 and PAR-2 slightly increased after the sham operation, whereas it markedly and significantly increased after balloon injury. Our observations suggest that balloon injury induced the receptor upregulation, thereby enhancing the contractile response before the establishment of vascular lesions. The local inflammation associated with the sham operation may also contribute to the receptor upregulation.


FLPe functions in zebrafish embryos.
To assay the efficiency of the FLP/FRT site-specific recombination system in Danio rerio, a construct consisting of a muscle-specific promoter driving EGFP flanked by FRT sites was developed. FLPe capped RNA was microinjected into transgenic single cell stage zebrafish embryos obtained by crossing hemizygous transgenic males with wild-type females. By 48 h post fertilization (hpf), the proportion of embryos displaying green fluorescence following FLPe RNA microinjection was significantly lower (7.7%; P < 0.001) than would be expected from a cross in the absence of the recombinase (50%). Embryos that retained fluorescence displayed marked mosaicism. Inheritance of the excised transgene in non-fluorescent, transgenic embryos was verified by PCR analysis and FLPe-mediated recombination was confirmed by DNA sequencing. Sperm derived from confirmed transgenic males in these experiments was used to fertilize wild-type eggs to determine whether germline excision of the transgene had occurred. Clutches sired by FLPe-microinjected males contained 0-4% fluorescent embryos. Transgenic males that were phenotypically wild-type produced no fluorescent progeny, demonstrating complete excision of the transgene from their germline. FLPe microinjected males that retained some fluorescent muscle expression produced a small proportion of fluorescent offspring, suggesting that in mosaic males not all germline cells had undergone FLPe-mediated transgene excision. Our results show that FLPe, which is derived from Saccharomyces cerevisiae, is an efficient recombinase in zebrafish maintained at 28.5°C.


[Severe domestic squalor].
People who live in domestic squalor and deny help may have a condition known as severe domestic squalor, previously Diogenes syndrome. The object of this article is to provide a review of incidence, possible etiology, clinical description and management of this condition. The article is based on literature retrieved through a non-systematic search in PubMed and the author's clinical experience. Severe domestic squalor may affect people of all ages, but is particularly prevalent among the elderly. Those affected live in severe squalor with garbage, rotting food, rats and mice, urine and faeces in furniture. Some tend to hoard. The annual incidence among persons above 60 years of age, referred to a specialist, is approximately 0.5 per 1000. True community prevalence is unknown. More than 50 % of cases have a concomitant diagnosis of dementia, schizophrenia or substance dependency. An association between frontal dysfunction and severe domestic squalor is sparsely, but increasingly documented. Those affected do not express concern about their situation and are unwilling to be helped. Cases are complex and very difficult to handle for general practitioners and district nurses. Respect for autonomy and a wish to help contradict each other. It is very difficult to help persons who live in severe domestic squalor. The incidence in Norway is unknown and should be determined.


Intermolecular interactions and charge transfer transitions in aromatic hydrocarbon-tetracyanoethylene complexes.
A comprehensive theoretical study of the electronically excited states in complexes between tetracyanoethylene (TCNE) and three aromatic electron donors, benzene, naphthalene and anthracene, was performed with a focus on charge transfer (CT) transitions. The results show that the algebraic diagrammatic construction method to second order (ADC(2)) provides excellent possibilities for reliable calculations of CT states. Significant improvements in the accuracy of the computed transition energies are obtained by using the scaled opposite-spin (SOS) variant of ADC(2). Solvent effects were examined on the basis of the conductor-like screening model (COSMO) which has been implemented recently in the ADC(2) method. The dielectric constant and the refractive index of dichloromethane have been chosen in the COSMO calculations to compare with experimental solvatochromic effects. The computation of optimized ground state geometries and enthalpies of formation has been performed at the second-order Møller-Plesset perturbation theory (MP2) level. By comparison with experimental data and with high-level coupled-cluster methods including explicitly correlated (F12) wave functions, the importance of the SOS approach is demonstrated for the ground state as well. In the benzene-TCNE complex, the two lowest electronic excitations are of CT character whereas in the naphthalene and anthracene TCNE complexes three low-lying CT states are observed. As expected, they are strongly stabilized by the solvent. Geometry optimization in the lowest excited state allowed the calculation of fluorescence transitions. Solvent effects lead to a zero gap between S1 and S0 for the anthracene-TCNE complex. Therefore, in the series of benzene-TCNE to anthracene a change from a radiative to a nonradiative decay mechanism to the ground state is to be expected.


Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.
Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.


In vitro antioxidant and in vivo antidepressant activity of green synthesized azomethine derivatives of cinnamaldehyde.
In this study, three (CS-1 to CS-3) azomethine derivatives of cinnamaldehyde were green synthesized, characterized, and their antioxidant and antidepressant activities were explored. The antioxidant effect of these compounds was initially performed in vitro using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay methods before subjecting them to in vivo experiments. Compounds showing potent antioxidant activity (CS-1 and CS-2) were investigated further for their antidepressant activity using the forced swim test (FST) and tail suspension test (TST). Ascorbic acid (AA) and fluoxetine (20 mg/kg, p.o) were used as reference drugs for comparison in the antioxidant and antidepressant experiments, respectively. It was observed that CS-2 and CS-3 exhibited highest DPPH (half maximal inhibitory concentration [IC50]: 16.22 and 25.18 μg/mL) and ABTS (IC50: 17.2 and 28.86 μg/mL) radical scavenging activity, respectively, compared to AA (IC50: 15.73 and 16.79 μg/mL) and therefore, both CS-2 and CS-3 were tested for their antidepressant effect using FST and TST as experimental models. Pretreatment of CS-2 and CS-3 (20 mg/kg) for 10 days considerably decreased the immobility time in both the FST and TST models. The antioxidant and antidepressant effect of CS-2 and CS-3 may be attributed to the presence of azomethine linkage in the molecule.


Heterodimetallic compounds assembled from ferrocenedicarboxylato and ferrocenecarboxylato ligands.
Heteropolynuclear organometallic compounds have been constructed by using two kinds of ferrocene-based ligands, 1,1'-ferrocenedicarboxylic acid (H(2)L(1)) and ferrocenecarboxylic acid (HL(2)). Reactions the ligand H(2)L(1) with copper(II) and nickel(II) salts, in the presence of pyridine, give a tetranuclear Cu(2)Fe(2) mixed-metallic box Cu(2)L(1)(2)(Py)(2)(DMF)(2)(H(2)O)(2) (1) and a tetranuclear heterobimetallic helix Ni(2)L(1)(2)(Py)(4)(H(2)O) (2), respectively. In these complexes, the ferrocene moieties show cisoid conformations which lead to the formation of the finite coordination geometry, i.e. to molecular complexes. Interactions of the ligand H(2)L(1) with lanthanide ions afford two-dimensional networks [La(2)L(1)(3)(CH(3)OH)(4)]( infinity ) (3), [Eu(2)L(1)(3)(H(2)O)(5)]( infinity ) (4), and [Gd(2)L(1)(3)(CH(3)OH)(2)(H(2)O)(3)]( infinity ) (5), respectively, in which transoid conformations of the ferrocene moiety provide opportunities to form infinite 2-D networks. It is suggested that the conformational freedom of the ferrocene moiety makes the ligand L(1) display different conformations and coordination modes in these complexes. In addition, the pi.pi interactions related to the ferrocene moieties were also found to stabilize the supramolecular architectures in the solid state. As a comparison, reaction of lanthanide ions with the ligand HL(2) resulted in three isostructural heterodinuclear windmill-shaped compounds Ln(2)L(2)(6)(CH(3)OH)(2)(H(2)O)(5) [Ln = La (6), Eu (7), and Gd (8)] by simply diffusing the solutions of lanthanide ions into the mixture of HL(2) and NaOH, respectively. Electrochemical properties of the ferrocene-containing complexes 1-8 are also investigated in the solution or solid state.


Naming actions and objects: cortical dynamics in healthy adults and in an anomic patient with a dissociation in action/object naming.
Neuropsychological studies have demonstrated that the production of nouns and verbs can be dissociated in aphasia. These reports have been taken as evidence for separate representations of nouns and verbs in the human brain. We used whole-head magnetoencephalography to record cortical dynamics of action and object naming in 10 healthy adults and in 1 anomic patient with superior naming of verbs compared with nouns due to a left posterior parietal lesion. A single set of 100 line drawings was used for both action and object naming. In normal subjects, the activation sequences in action and object naming were essentially identical, advancing from the occipital to posterior temporoparietal and further to the left frontal cortex, without consistent involvement of the classical left inferior frontal (Broca) and temporal (Wernicke) language areas. In the anomic patient, pronounced differences between action and object naming emerged in the left hemisphere. The activation sequence was disrupted at the level of the damaged parietal cortex and did not reach the left frontal cortex even in the relatively easier action naming. The more severely impaired object naming was associated with exceptionally strong and early activation of the left inferior frontal cortex (Broca) and subsequent pronounced activation of the left middle temporal cortex, silent in action naming. Verb and noun retrieval thus utilized a spatiotemporally similar neuronal network in healthy individuals. A clear dissociation in cortical correlates of verb and noun retrieval only became evident in our anomic patient, in whom damage to the language network has resulted in disproportionately worse performance in object than action naming.


Two novel mutations in phenylalanine hydroxylase gene and in vitro expression analysis on mutation Arg252Gln.
We report novel mutations in exon 7 of human phenylalanine hydroxylase (PAH) gene of phenylketonuria (PKU) in southern Chinese, analysed by using PCR-DGGE (denaturing gradient gel electrophoresis), solid phase DNA sequencing and in vitro expression. One of the 2 novel mutations, IVS6nt-1, is an intron-exon junctional mutation which results a splicing defect in mRNA. Arg252Gln is another novel mutation with residual PAH activity only 24% compared to wild type in in vitro mutagenesis and expression in Cos-1 cell. Other 3 known mutations and polymorphism including Arg241Cys, Arg243Gln and Val245Val (GTG to GTA) together with these novel mutations composed the mutational profile of exon 7 in the PAH gene of PKUs in this populations.


Performance of ProEx C and PreTect HPV-Proofer E6/E7 mRNA tests in comparison with the hybrid capture 2 HPV DNA test for triaging ASCUS and LSIL cytology.
The clinical usefulness of the ProEx C (Becton Dickinson) and PreTect HPV-Proofer E6/E7 mRNA tests (Proofer; Norchip) for the triage of ASCUS and LSIL cytology was determined in comparison with the Hybrid Capture 2 HPV DNA test (HC2; Qiagen). The study population consisted of women with a history of abnormal cytology referred to colposcopy. Histology-confirmed CIN 2+ served as the disease endpoint. The study was based on 1,360 women (mean age 30.7 years), of whom 380 had CIN 2+. Among 315 with ASCUS (CIN 2+, n = 67), the sensitivities of ProEx C, Proofer, and HC2 to detect CIN 2+ were, 71.6, 71.6, and 95.5%, respectively, with a corresponding specificity of 74.6, 74.2, and 35.1%. Among 363 with LSIL (CIN 2+, n = 108), the sensitivities of ProEx C, Proofer, and HC2 were, 67.6, 74.1, and 96.3%, respectively, with a corresponding specificity of 60, 68.2, and 18.4%. Among 225 HC2-positive ASCUS (CIN 2+, n = 64), 105 tested positive by ProEx C, reducing colposcopy referral by 53.3% and detecting 71.9% of CIN 2+; Proofer was positive in 112/225, reducing colposcopy referral by 50.2% and detecting 75.0% of CIN 2+. Among 312 HC2-positive LSIL (CIN 2+, n = 104), 160 tested positive by ProEx C, reducing coloposcopy referral by 48.7% and detecting 66.3% of CIN 2+; Proofer was positive in 159/312, reducing colposcopy referral by 49.0% and detecting 75.0% of CIN 2+. In conclusion, both ProEx C and Proofer have a similar performance profile with a significantly higher specificity but lower sensitivity than HC2 for the detection of CIN 2+. Consequently, although they can reduce colposcopy referral, they will miss a proportion of CIN 2+ cases. This is a major limitation and should be taken into account if these tests are considered for ASCUS or LSIL triage.


Incidence of axillary recurrence in 344 sentinel node negative breast cancer patients after intermediate follow-up. A prospective study into the accuracy of sentinel node biopsy in breast cancer patients.
Sentinel lymph node biopsy (SLNB) has been validated in the treatment of breast carcinoma and is considered to stage the axilla adequately in this disease. However, long-term follow-up data are scarce. We evaluated the results of SLNB with respect to loco-regional failures in the axilla in SN-negative patients with invasive breast carcinoma and analysed their causal factors. Between 1997 and May 2004, 656 patients without clinically palpable lymph nodes were included in our study. Data with regard to demographics, diagnostics, therapy and follow up were gathered prospectively from all patients. Patients treated after May 2004 were excluded from this study to permit at least one year of follow-up. Out of the 656 patients, 344 patients with a negative sentinel lymph node biopsy did not undergo axillary dissection and were followed up clinically. Median follow up was 43 months. In 3 patients (0.9%) axillary recurrences developed. All three patients subsequently underwent a completion axillary dissection, chemotherapy and radiotherapy. The low rate of clinical axillary recurrence after an intermediate follow up period suggests that a negative SN biopsy accurately reflects the nodal stage in patients with breast cancer.


Patient-reported nonadherence to HAART is related to protease inhibitor levels.
To compare self-reported nonadherence with antiretroviral therapy (ART) with predose plasma levels of protease inhibitor (PI). A cross-sectional study of consecutive patients from a university-based HIV clinic in Rome, Italy, was conducted. One hundred and forty HIV-infected patients were prescribed regimens containing ritonavir or indinavir. A patient questionnaire assessing knowledge of treatment regimen, adherence behavior, reasons for taking and missing therapy, factors influencing adherence, and health behaviors was administered. A predose PI plasma level was measured concurrently. By patient report, 12% missed at least one dose "yesterday," and 24% missed doses in the last 3 days; 14% had a predose plasma concentration below the assay limit of quantitation (2 ritonavir and 18 indinavir samples). Confusion, poor psychological well-being, long office wait, running out of drugs between visits, having relatives to remind the patient to take medication, children, and alteration of sense of taste were related to unquantifiable predose levels of PI. In multivariable analysis, reported nonadherence (odds ratio [OR], 15.8; 95% confidence interval [CI], 4.0-63.3) and confusion (OR, 9.9; 95% CI, 1.4-69.6) were related to unquantifiable predose levels of PI. Self-report of missing a dose of antiretroviral medication "yesterday" was related to an unmeasurable plasma PI level.


Septohippocampal pathways contribute to system consolidation of a spatial memory: sequential implication of GABAergic and cholinergic neurons.
Studies of the neuropharmacological substrates of spatial memory formation have focused on the contribution of septohippocampal pathways. Although these pathways include, among others, cholinergic and GABAergic fibers innervating the hippocampus, research has essentially been oriented towards the role of their cholinergic component. Recently, a few studies investigated the role of GABAergic septohippocampal projections. These only focused on almost immediate or recent memory and yielded discrepant results. GABAergic lesions impaired learning or had no effects. Given the role of the hippocampus in memory consolidation and the potential modulatory influence of the septum on hippocampal function, it is relevant to study the role of the septohippocampal interface in memory stabilization. We performed investigations with relatively selective lesions of GABAergic (using oxerin-saporin) or/and cholinergic (using 192 IgG-saporin) medial septum/vertical limb of the diagonal band of Broca (MS/vDBB) neurons in rats, and assessed acquisition of a spatial memory and its subsequent recall in the water maze. Following a 6-day training phase during which all groups improved performance to comparable levels, retention was tested 1, 5, or 25 days later. At the 1-day delay, all groups performed above chance and did not differ significantly among each other. At the 5-day delay, only rats with GABAergic or combined lesions exhibited a retention deficit. At the 25-day delay, all three lesion groups performed at chance level; in these groups, performance was significantly lower than that found in sham-operated rats. Immunochemical and histochemical verifications of the lesion extent/selectivity showed extensive GABAergic damage after intraseptal orexin-saporin infusions or cholinergic damage after 192 IgG-saporin infusions, with relatively limited damage to the other neurotransmitter system. Our data show that GABAergic and cholinergic septohippocampal neurons both contribute to memory stabilization, and could do so in a sequential way: GABAergic processes could be engaged at an earlier stage than cholinergic ones during system consolidation of a spatial memory.


[A 40-year-old female patient with seronegative autoimmune hepatitis following a newly acquired hepatitis B infection].
We report the case of a 40-year-old female patient admitted at our clinic because of recent onset jaundice and elevated transaminases. Two months before admission the patient had unprotected sexual contact with a potential hepatitis B-infected man. Virological screening performed in our clinic revealed IgM antibodies against hepatitis B virus core protein (anti-HBc-IgM) and elevated HBV-DNA. Our first diagnosis was an acute hepatitis B virus infection. During her stay at our clinic the patient achieved HBe seroconversion and a loss of HBV-DNA. Nevertheless the transaminases remained high and jaundice persisted. The histological examination of the liver biopsy showed interface hepatitis with plasma cells as the characteristic signs of autoimmune hepatitis. On that basis we started an immunosuppressive therapy with prednisolone in parallel with a prophylactic lamivudine therapy and after two weeks there was a complete resolution of jaundice and a normalisation of transaminases. In conclusion, we present a rare case report of an autoimmune hepatitis as a result a newly acquired hepatitis B infection. This case report highlights the relationship between viral infection and autoimmunity within the liver.


Coring-type laparoscopic resection of a cavitated non-communicating rudimentary horn under hysteroscopic assistance.
Non-communicating accessory uterine horns with an endometrial cavity are the most common and clinically significant unicornuate subtype of Müllerian duct abnormality. They are generally associated with symptoms of dysmenorrhea, dyspareunia, infertility, endometriosis, adhesions, and life-threatening cornual pregnancy. Treatment options include surgical resection of the rudimentary horn, hysteroscopic recanalization, and endometrial ablation. Currently, laparoscopic resection is the recommended treatment choice. Dissection of the rudimentary horn from the unicornuate uterus is the most challenging part of this procedure and may compromise the remaining unicornuate uterus wall. Here we describe a case of laparoscopic coring-type resection of a non-communicating functional rudimentary horn firmly attached to the unicornuate uterus, by using hysteroscopic assistance. The use of hysteroscopy, adjunct to laparoscopy, facilitates the coring-type resection and may strengthen the remaining myometrial scar.


Reducing the stimulation of CD8+ T cells during infection with intracellular bacteria promotes differentiation primarily into a central (CD62LhighCD44high) subset.
During infection with lymphocytic choriomeningitis virus, CD8(+) T cells differentiate rapidly into effectors (CD62L(low)CD44(high)) that differentiate further into the central memory phenotype (CD62L(high)CD44(high)) gradually. To evaluate whether this CD8(+) T cell differentiation program operates in all infection models, we evaluated CD8(+) T cell differentiation during infection of mice with recombinant intracellular bacteria, Listeria monocytogenes (LM) and Mycobacterium bovis (BCG), expressing OVA. We report that CD8(+) T cells primed during infection with the attenuated pathogen BCG-OVA differentiated primarily into the central subset that correlated to reduced attrition of the primed cells subsequently. CD8(+) T cells induced by LM-OVA also differentiated into central phenotype cells first, but the cells rapidly converted into effectors in contrast to BCG-OVA. Memory CD8(+) T cells induced by both LM-OVA as well as BCG-OVA were functional in that they produced cytokines and proliferated extensively in response to antigenic stimulation after adoptive transfer. During LM-OVA infection, if CD8(+) T cells were guided to compete for access to APCs, then they received reduced stimulation that was associated with increased differentiation into the central subset and reduced attrition subsequently. Similar effect was observed when CD8(+) T cells encountered APCs selectively during the waning phase of LM-OVA infection. Taken together, our results indicate that the potency of the pathogen can influence the differentiation and fate of CD8(+) T cells enormously, and the extent of attrition of primed CD8(+) T cells correlates inversely to the early differentiation of CD8(+) T cells primarily into the central CD8(+) T cell subset.


Intraligand charge-transfer excited states in Re(I) complexes with donor-substituted dipyridophenazine ligands.
The donor-acceptor ligands 11-(4-diphenylaminophenyl)dipyrido[3,2-a:2',3'-c]phenazine (dppz-PhNPh2) and 11-(4-dimethylaminophenyl)dipyrido[3,2-a:2',3'-c]phenazine (dppz-PhNMe2), and their rhenium complexes, [Re(CO)3X] (X = Cl(-), py, 4-dimethylaminopyridine (dmap)), are reported. Crystal structures of the two ligands were obtained. The optical properties of the ligands and complexes are dominated by intraligand charge transfer (ILCT) transitions from the amine to the dppz moieties with λabs = 463 nm (ε = 13 100 M(-1) cm(-1)) for dppz-PhNMe2 and with λabs = 457 nm (ε = 16 900 M(-1) cm(-1)) for dppz-PhNPh2. This assignment is supported by CAM-B3LYP TD-DFT calculations. These ligands are strongly emissive in organic solvents and, consistent with the ILCT character, show strong solvatochromic behavior. Lippert-Mataga plots of the data are linear and yield Δμ values of 22 D for dppz-PhNPh2 and 20 D for dppz-PhNMe2. The rhenium(I) complexes are less emissive, and it is possible to measure resonance Raman spectra. These data show relative band intensities that are virtually unchanged from λexc = 351 to 532 nm, consistent with a single dominant transition in the visible region. Resonance Raman excitation profiles are solvent sensitive; these data are modeled using wavepacket theory yielding reorganization energies ranging from 1800 cm(-1) in toluene to 6900 cm(-1) in CH3CN. The excited state electronic absorption and infrared spectroscopy reveal the presence of dark excited states with nanosecond to microsecond lifetimes that are sensitive to the ancillary ligand on the rhenium. These dark states were assigned as phenazine-based (3)ILCT states by time-resolved infrared spectroscopy. Time-resolved infrared spectroscopy shows transient features in which Δν(CO) is approximately -7 cm(-1), consistent with a ligand-centered excited state. Evidence for two such states is seen in mid-infrared transient spectra.


Intact or impaired? The understanding of give-and-take interactions in children with autism spectrum disorder.
Understanding and predicting others' behavior in a dynamic and rapidly changing world is a fundamental aspect of social interactions. However, it remains unclear as to whether children with autism spectrum disorder (ASD) could understand and predict goal-directed social actions. To investigate the understanding of give-and-take interactions in children with ASD with the use of eye tracking. Experiment 1 and 2 investigated the understanding of giving and taking respectively in 5-to 8-year-old Chinese children with ASD and typically developing children by using the eye-tracking technology. We found that children with ASD could predict actions, but they were less proficient in processing give-and-take interactions. Moreover, children with ASD showed impaired understanding of giving but not taking. These results indicate that the basic mechanisms of action prediction are intact in children with ASD whereas there may be deficits in the top-down social processing of the giving gesture.


Epidemiology, production losses, and control measures associated with an outbreak of avian influenza subtype H7N2 in Pennsylvania (1996-98).
An outbreak of H7N2 low-pathogenicity (LP) avian influenza (AI) occurred in a two-county area in Pennsylvania from December of 1996 through April of 1998. The outbreak resulted in infection of 2,623,116 commercial birds on 25 premises encompassing 47 flocks. Twenty-one (one premise with infection twice) of the twenty-five infected premises housed egg-laying chickens and one premise each had turkeys, layer pullets, quail, and a mixed backyard dealer flock. Despite dose proximity of infected flocks to commercial broiler flocks, no infected broilers were identified. Experimentally, when market age broilers were placed on an influenza-infected premise they seroconverted and developed oviduct lesions. The outbreak was believed to have originated from two separate introductions into commercial layer flocks from premises and by individuals dealing in sales of live fowl in the metropolitan New York and New Jersey live-bird markets. Source flocks for these markets are primarily in the northeast and mid-Atlantic areas, including Pennsylvania. Mixed fowl sold include ducks, geese, guinea hens, quail, chukar partridges, and a variety of chickens grown on perhaps hundreds of small farms. Infections with the H7N2 AI virus were associated with variable morbidity and temporary decreases in egg production ranging from 1.6% to 29.1% in commercial egg-laying chickens. Egg production losses averaged 4.0 weeks duration. Mortality ranged from 1.5 to 18.3 times normal (mean of 4.3 times normal). Duration of mortality ranged from 2 to 13 weeks (average of 3.9 weeks) in flocks not depopulated. Lesions observed were primarily oviducts filled with a mucous and white gelatinous exudates and atypical egg yolk peritonitis. Quarantine of premises and complete depopulation were the early measures employed in control of this outbreak. Epidemiological studies suggested that depopulation furthered the spread of influenza to nearby flocks. Thereafter, later control measures included quarantine, strict biosecurity, and controlled marketing of products.


The effects of rhythm training on tennis performance.
Rhythm training is an integral part of sports. The purposes of the study were to analyze the effects of rhythm training on tennis performance and rhytmic competence of tennis players, to compare the improvement levels of tennis specific and general rhythm training and to examine the effects of shorter and longer tempos on rhythmic competence. Thirty university students whose mean score of International Tennis Number (ITN) was 7.3 (±0.9) were divided randomly into three sub-groups: Tennis Group, General Rhythm Training Group and Tennis-Specific Rhythm Training Group. The experimental procedure lasted 8 weeks. During this period, all groups had the same tennis training twice a week. The Tennis Group had regular tennis training sessions. In addition to regular tennis training sessions, the General Rhythm Training Group followed the general rhythm training sessions and the Tennis-Specific Rhythm Training Group had tennis-specific rhythm training. The measurement instruments were ITN, Rhythmic Competence Analysis Test and Untimed Consecutive Rally Test. The results indicated that participation in tennis-specific or general rhythm training resulted in progress in tennis playing levels, forehand consistency performance and rhythmic competence of the participants. On the other hand, attendance to the regular 8-week tennis training was enough to solely increase the tennis playing level but not sufficient to develop forehand consistency performance and rhythmic competence. Although the participants in the TRTG had better improvement scores than the ones in the GRTG, no significant difference was found between the rhythm training groups. The results also revealed that participants exhibited higher rhythmic competence scores on fast tempo compared to slow tempo.


Impacts of the Master Settlement Agreement on the tobacco industry.
To assess effects of the Master Settlement Agreement (MSA) and the four individual state settlements on tobacco company decisions and performance. 10-K reports filed with the US Securities and Exchange Commission, firm and daily data from the Center for Research in Security Prices, stock price indices, market share and advertising data, cigarette export and domestic consumption data, and newspaper articles were used to assess changes before (1990-98) and after (1999-2002) the MSA was implemented. Five major tobacco manufacturers in the USA. Stockholder returns, operating performance of defendant companies, exports, market share of the original participants in the MSA, and advertising/promotion expenditures. Returns to investments in the tobacco industry exceeded returns from investments in securities of other companies, using each of four indexes as comparators. Domestic tobacco revenues increased during 1999-2002 from pre-MSA levels. Profits from domestic sales rose from levels prevailing immediately before the MSA. There is no indication that the MSA caused an increase in tobacco exports. Total market share of the original participating manufacturers in the MSA decreased. Total advertising expenditures by the tobacco companies increased at a higher rate than the 1990-98 trend during 1999-2002, but total advertising expenditures net of spending on coupons and promotions decreased. The experience during the post-MSA period demonstrates that the MSA did no major harm to the companies. Some features of the MSA appear to have increased company value and profitability.


Increasing baseline aortic valve peak flow velocity is associated with progression of aortic valve stenosis in osteoporosis patients-a possible link to low vitamin D status.
The purpose of this study was to investigate the morphological characteristics of the aortic valve and identify factors associated with the progression of aortic valve stenosis (AS) in osteoporosis patients. In this single-center prospective cohort study, we recruited 10 patients (mean age: 75 ± 7 years, 90% female) who were taking anti-resorptive medicines at the outpatient clinic of University of Miyazaki Hospital, Japan. Baseline assessments, including transthoracic echocardiogram, blood sampling, and dual energy X-ray absorptiometry, were performed. Follow-up assessments were conducted at 6, 12, 18, and 24 months. During the 2-year follow-up, three patients with aortic valve peak flow velocity (AV PFV) ≥2 m/s at baseline developed moderate AS, which is defined as AV PFV ≥3 m/s. However, seven patients with AV PFV <2 m/s did not exhibit any progression of AS. There were significant variations in terms of bone mineral density, T-score values, and biomarkers associated with bone turnover (i.e., bone alkaline phosphatase, tartrate-resistance acid phosphatase-5b) among the enrolled patients, but none of these factors were found to be associated with the progression of AS. All patients exhibited low vitamin D status, with a median level of 16.1 ng/mL (25th percentile, 9.7 ng/mL; 75th percentile, 23 ng/mL). The baseline levels of AV PFV values were negatively correlated with 25-hydroxyvitamin D levels, determined by univariate linear regression analysis (beta coefficient = -0.756, 95% confidence interval, -0.136 ̶ -0.023, p = 0.011). Our data suggest that low vitamin D status might be a potential risk factor for the progression of AS in osteoporosis patients undergoing treatment with anti-resorptive medicines. Elderly patients with osteoporosis patients exhibited a subset of aortic valve stenosis. Our data suggest that the baseline aortic valve peak flow velocity predicts the progression of aortic valve stenosis, and there might be an association between the progression and the co-existing low vitamin D status in these patients.


Implementation of a compact, four-stage, scalable optical interconnect for photonic backplane applications.
We report on the implementation of a dense 512-beam free-space optical interconnect linking four optoelectronic VLSI chips at the backplane level. The system presented maximizes the positioning tolerances of the components by use of slow f-number (f/16) Gaussian beams and oversized apertures. A beam-clustering scheme whereby a 4 x 4 array of beams is transmitted by each minilens is used to provide a high channel density. A modular approach is used to decrease the number of degrees of freedom in the system and achieve passive alignment of the modules in the final integration phase. A design overview as well as assembly and experimental results are presented.


Vegetarian diets across the lifecycle: impact on zinc intake and status.
Optimal zinc status is an important consideration when evaluating the nutritional adequacy of vegetarian diets. In the absence of animal tissue sources of zinc and with increased intake of inhibitors of zinc absorption, phytic acid in particular, the bioavailability of zinc is thought to be lower from vegetarian as compared to omnivorous diets. The aim of this chapter is to review the research that examines the effects of vegetarian compared to omnivorous diets on zinc intake and zinc status in the elderly, adults, children, pregnancy, and lactation. A narrative review of the published literature was undertaken, focusing on observational studies in humans that reported zinc intake and biomarkers of zinc status at various stages of the life cycle. Compared to their respective nonvegetarian control groups, adult male and female vegetarians have lower dietary zinc intakes and serum zinc concentrations. However in the elderly, children, and in women during pregnancy and lactation, there is insufficient evidence to determine whether zinc intake and status are lower in vegetarians compared to omnivores. Inconsistencies in study findings reflect variations inherent in the definition of vegetarian diets, and in many instances compromised statistical power due to a small sample size. Improved methods for the assessment of zinc status are required to determine whether homeostatic responses are sufficient to maintain an adequate zinc status in vegetarians, particularly during times of increased requirement. Appropriate dietary advice to increase the zinc content and bioavailability of vegetarian diets throughout the life cycle is prudent.


Growth and composition of nanostructured and nanoporous cerium oxide thin films on a graphite foil.
The morphology and composition of CeOx films prepared by r.f. magnetron sputtering on a graphite foil have been investigated mainly by using microscopy methods. This study presents the formation of nanocrystalline layers with porous structure due to the modification of a carbon support and the formation of cerium carbide crystallites as a result of the deposition process. Chemical analyses of the layers with different thicknesses performed by energy dispersive X-ray spectroscopy, electron energy loss spectroscopy and X-ray photoelectron spectroscopy have pointed to the reduction of the cerium oxide layers. In the deposited layers, cerium was present in mixed Ce(3+) and Ce(4+) valence. Ce(3+) species were located mainly at the graphite foil-CeOx interface and the chemical state of cerium was gradually changing to Ce(4+) going to the layer surface. It became more stoichiometric in the case of thicker layers except for the surface region, where the presence of Ce(3+) was associated with oxygen vacancies on the surface of cerium oxide grains. The degree of cerium oxide reduction is discussed in the context of particle size.


Transplantation of islet cells across major histocompatibility barriers after total lymphoid irradiation and infusion of allogeneic bone marrow cells.
Diabetic Lewis rats (AgB1/L) were evaluated as recipients of allogeneic Wistar-Furth (AgB2/2) isolated adult islets without the use of standard recipient immunosuppression. One group was treated with fractionated total lymphoid irradiation (TLI) and Wistar-Furth bone marrow cell reconstitution to proven chimerism prior to islet transplantation. This group returned to a prediabetic state following Wistar-Furth islet transplantation without any evidence of rejection for 100 days posttransplant. A second group of Lewis rats received only TLI without bone marrow treatment. They gave a varying result following islet transplantation with one recipient showing evidence of prolonged islet survival. A third chimeric control group did not receive isolated islets and did not alter their diabetic state. A fourth group was not given TLI nor donor bone marrow cells and uniformly rejected their allogeneic islets by 7 days. Thus, allogeneic adult islets will survive across major rat histocompatibility barriers using TLI and donor bone marrow chimerism as the only form of immunosuppression.


Third-generation in situ hybridization chain reaction: multiplexed, quantitative, sensitive, versatile, robust.
In situ hybridization based on the mechanism of the hybridization chain reaction (HCR) has addressed multi-decade challenges that impeded imaging of mRNA expression in diverse organisms, offering a unique combination of multiplexing, quantitation, sensitivity, resolution and versatility. Here, with third-generation in situ HCR, we augment these capabilities using probes and amplifiers that combine to provide automatic background suppression throughout the protocol, ensuring that reagents will not generate amplified background even if they bind non-specifically within the sample. Automatic background suppression dramatically enhances performance and robustness, combining the benefits of a higher signal-to-background ratio with the convenience of using unoptimized probe sets for new targets and organisms. In situ HCR v3.0 enables three multiplexed quantitative analysis modes: (1) qHCR imaging - analog mRNA relative quantitation with subcellular resolution in the anatomical context of whole-mount vertebrate embryos; (2) qHCR flow cytometry - analog mRNA relative quantitation for high-throughput expression profiling of mammalian and bacterial cells; and (3) dHCR imaging - digital mRNA absolute quantitation via single-molecule imaging in thick autofluorescent samples.


Temporal trends of ventilator-associated pneumonia incidence and the effect of implementing health-care bundles in a suburban community.
Recent changes in critical care delivery, including the widespread implementation of health-care bundles, were aimed at reducing complications of critical illness, in particular ventilator-associated pneumonia (VAP), but no population-based study evaluated its effectiveness. Using a previously validated electronic medical record database, we identified adult (≥ 18 years old) critically ill patients from Olmsted County, Minnesota, requiring mechanical ventilation for ≥ 48 h from January 2003 to December 2009. Trained intensivists identified cases of VAP according to different established clinical definitions. The incidence and outcome of VAP was compared before and after implementation of the so-called "VAP bundle." The median age, severity of illness, proportion of surgical patients, and patients with neurologic disease increased over time (P < .05 for trend in all). Regardless of the definition used, the VAP rate remained similar throughout the study period and did not change with the introduction of the VAP bundle. According to previous Centers for Disease Control and Prevention criteria, the yearly estimates of the VAP incidence ranged between 7.1 and 10.4 cases per 1,000 ventilator-days, with an age-adjusted incidence of 3.1 vs 5.6 per 100,000 population (P = .54 for trends). Standardized hospital mortality ratio of patients at high risk to develop VAP significantly decreased from 1.7 (95% CI, 0.8-3.0) to 0.7 (95% CI, 0.3-1.4; P = .0003 for trend). The incidence of VAP was unaffected by the implementation of the VAP bundle. Secular changes in hospital mortality are unlikely to be attributed to the VAP bundle per se.


New Insights into Prospective Health Potential of ω-3 PUFAs.
Docosahexaenoic acid and eicosapentaenoic acid are the two essential long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs) promoting human health which are obtained from diet or supplementation. The eicosanoids derived from ω-6 and ω-3 PUFAs have opposite characteristics of pro- and anti-inflammatory activities. The proinflammatory effects of ω-6 PUFAs are behind the pathology of the adverse health conditions of PUFA metabolism like cardiovascular diseases, neurological disorders, and inflammatory diseases. A balanced ω-6 to ω-3 ratio of 1-4:1 is critical to prevent the associated disorders. But due to modern agricultural practices, there is a disastrous shift in this ratio to 10-20:1. This review primarily aims to discuss the myriad health potentials of ω-3 PUFAs uncovered through recent research. It further manifests the importance of maintaining a balanced ω-6 to ω-3 PUFA ratio. ω-3 PUFAs exhibit protective effects against diabetes mellitus-associated complications including diabetic retinopathy, diabetic nephropathy, and proteinuria. COVID-19 is also not an exception to the health benefits of ω-3 PUFAs. Supplementation of ω-3 PUFAs improved the respiratory and clinical symptoms in COVID-19 patients. ω-3 PUFAs exhibit a variety of health benefits including anti-inflammatory property and antimicrobial property and are effective in protecting against various health conditions like atherosclerosis, cardiovascular diseases, diabetes mellitus, COVID-19, and neurological disorders. In the present review, various health potentials of ω-3 PUFAs are extensively reviewed and summarized. Further, the importance of a balanced ω-6 to ω-3 PUFA ratio has been emphasized besides stating the diverse sources of ω-3 PUFA.


Implications of continuity of care on infant caloric intake in the neonatal intensive care unit.
To estimate the association of continuity of neonatologist care with caloric intake and growth velocity (GV) in very low birth weight (VLBW) infants. We created a daily continuity index (DCI) defined as the number of days the neonatologist worked in the previous week. We estimated the independent associations between this index and infants' daily caloric intake (kcal/kg/day) and GV (g/kg/day) through the first 6 weeks of life using regression analyses. Twenty-eight neonatologists cared for 115 infants over 4643 patient-days. The DCI was independently associated with increased caloric intake (β = 1.27 kcal/kg/day per each day of continuity, p < 10-4); this effect was magnified (β = 3.33, p < 10-4) in the first 2 weeks. No association was observed between the index and GV. Neonatologist continuity may contribute to caloric intake in VLBW infants. Quality metrics focused on this area of health care delivery warrant further discovery.


Andean leishmaniasis in Ecuador caused by infection with Leishmania mexicana and L. major-like parasites.
Between 1986 and 1988, epidemiologic studies were carried out in a small rural community in an Andean region of Ecuador, where cutaneous leishmaniasis is highly endemic. A total of 25 human cases, positive for Leishmania parasites by culture and/or smear, were examined. Fourteen of the cases were in infants less than one year of age, suggesting intradomiciliary transmission of the disease. Clinically, many of these cases were similar to descriptions of "uta," a form of cutaneous leishmaniasis which occurs in Andean regions of Peru and is reported caused by L. peruviana. Of the 11 positive cultures obtained from human cases in the present study, eight were identified by molecular characterization as L. mexicana and three were identified as L. major-like. Two additional isolates of L. mexicana were also made from an infected dog and from a sand fly, Lutzomyia ayacuchensis, living in the region, thus implicating the latter species as possible reservoir and vector, respectively, of L. mexicana in this highland community. The significance and validity of recent isolates of L. major-like parasites from the New World are also discussed.


Endoanorectal ultrasonography.
Endoanorectal ultrasonography (EARUS) may be used for diagnosing various anorectal disorders. EARUS is easy to perform, has a short learning curve, and causes less discomfort than routine digital examination. Anal sphincters can be clearly visualized, and one can easily distinguish between the internal (hypoechoic) and external (hyperechoic) anal sphincters. Other pelvic floor structures, like the puborectalis muscle, can also be visualized. The use of contrast agents can increase the accuracy of EARUS in the assessment of perianal fistulae. In addition, EARUS is an excellent alternative to expensive magnetic resonance imaging. Besides its use in incontinence and perianal sepsis, the presence of slight or massive submucosal invasion in early rectal cancer may be imaged in greater detail. With 3-dimensional EARUS, it is possible to diagnose the anorectal diseases, in multiplane, with high spatial resolution, adding important information about the therapeutic decision. The normal sonographic anatomy of the anorectum, sonographic findings of anorectal diseases, and indications and limitations of endosonography with complementary techniques such as transvaginal and transperineal ultrasound are reviewed in this article.


IL-17 Inhibitors and Inflammatory Bowel Diseases: A Postmarketing Study in Vigibase.
Several gastrointestinal symptoms and chronic inflammatory bowel diseases (IBDs) have been reported after therapy with IL-17 inhibitors. To date, however, no study has shown a clear association between these drugs and IBD onset. We searched on Vigibase, the worldwide pharmacovigilance database, to investigate reporting prevalence, characteristics, and prognosis of all gastroenterological adverse events in patients treated with IL-17 inhibitors. In total, 1,129 gastrointestinal Individual Case Safety Reports (ICSRs) were identified, including 850 IBD (42.5% Crohn's disease, 31.9% ulcerative colitis, and 25.6% undifferentiated IBD) and 279 colitis (mainly undifferentiated colitis (79.2%), and microscopic colitis (10.4%)). ICSRs were associated with secukinumab (SEC, 83.6%) or ixekizumab (IXE, 16.3%), whereas only one colitis occurred with brodalumab (0.1%). Most IBD and colitis cases were detected within 6 months from therapy start in both the SEC (68.8% and 73.5%) and IXE groups (100% and 66.7%). Patients' outcomes were reported in 428 ICSRs (37.9%). Complete or ongoing recovery from symptoms was detected in about two-thirds of patients experiencing IBD (59.5%) or colitis (64.2%), whereas in the other cases, there was no recovery (33.9% and 29.5%) or there were sequelae (5.4% and 4.2%). Fatal events occurred in four patients (1.2%) in the IBD group (3 after SEC and on1e with IXE) and two SEC-treated subjects in the colitis group (2.1%). Treatment with IL-17 inhibitors is associated with a relevant number of exacerbations and new onset of IBD and colitis. Careful evaluation of gastrointestinal symptoms and the monitoring of intestinal inflammatory biomarkers should be recommended before prescribing these drugs.


Plating of proximal fracture of the humerus: a study of 30 cases.
In recent years, plate osteosynthesis with angular stable implants is frequently used for severely displaced three- and four-part proximal humeral fractures. The aim of this study is to evaluate early results of these fractures treated with insertion of LCP or Philos plates. We present results in 30 cases of proximal humeral fractures, 17 with 3 parts according to Neer and 13 with 4 parts, treated with Locking Compression Plates (LCP, 14 cases) and Philos plates (16) by the deltopectoral approach. Patients were checked with standard X-rays and clinical evaluation, according to the Constant-Murley shoulder score, Individual Constant score and Relative Constant score. Mean follow-up time was 21 months (range 6-42 months). The mean Constant-Murley shoulder scores were Pain 10.6 (3-15), Activities of Daily Living 15.3 (2-20), Range of Motion 26.8 (12-40) and Power 10.3 (3-25) and Total 63 (25-97). The Individual Constant score was 68.6% (27-98%) and the Relative Constant score 85.4% (36-130%). Fractures in 3 parts (of the surgical or anatomic humeral neck and major tubercle) had a mean Constant score of 69.1 (17 cases), but this fell to 55 (13 cases) in those in 4 parts (neck, major and lesser tubercles). Late necrosis of the humeral head occurred in two cases, both with 4-part breaks. We thus believe that 3-part fractures, in which both reduction and stable osteosynthesis are easier, show favourable prognosis and should be clearly distinguished from 4-part ones during assessments. The deltopectoral approach offers good exposure and is especially recommended in 4-part fractures, also because it provides a good view of the lesser tubercle. The osteosynthesis must be stable if early mobilisation of the shoulder and proper recovery of range of motion are to be achieved. As well as reduction and stabilisation of the tubercles, it is also important to restore the neck/shaft angle and stabilise it with oblique screws fitting the plate to avoid varus malposition.


The crisis in Cochrane: Evidence Debased Medicine.
The mission of the Cochrane Collaboration, established in 1993, was to systematically review medical evidence with a view to producing the best quality and trustworthy evidence. Twenty-five years later, it is in a crisis that centres on the dismissal one of its founders and the question of access to clinical trial data. The original mission aimed at improving health. In the face of stalling life expectancies, the stakes in the current crisis could not be higher. This essay looks at the crisis in the context of the disastrous effects of medication for paediatric depression on children as a consequence of the suppression of adverse findings from clinical trials.


Long-term treatment of severe hypertension with minoxidil, propranolol and furosemide.
Thirteen patients with severe hypertension were treated with combined minoxidil, propranolol, and furosemide (mean daily doses 33 mg, 475 mg, and 578 mg, respectively) for nine to twenty-five months (mean 13.8). Average mean blood pressure while on aggressive therapy with conventional medication was 144 +/- 14 mm Hg; on minoxidil and propranolol it was 108 "/- 10 mm Hg (P less thator to optimum blood pressure control and required large doses of furosemide to control. Propranolol blunted the reflex tachycardia associated with arteriolar dilator therapy but all patients continued with a clinically hyperdynamic circulation. Seven of seven had elevated ejection fractions on echocardiogram, and two of three had elevated cardiac indices. Three of three who had heart catheterization had pulmonary hypertension which was aggravated by exercise. An additional three patients on hydralazine, propranolol, and furosemide also had pulmonary hypertension suggesting this is not unique to minoxidil. Two of thirteen developed pericardial effusions. Renal function improved in three and worsened in three.


Treatment effect of canagliflozin for patients on therapy for heart failure: Pooled analysis of the CANVAS program and CREDENCE trial.
Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that has been shown to reduce cardiovascular events in diabetic patients with and without heart failure (HF). Whether the clinical benefits and safety profile of canagliflozin are different in those on a beta blocker and an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (BB + RAASi) is unknown. We pooled participants with HF at baseline from the CANVAS Program and CREDENCE trial and assessed major adverse cardiovascular events and its components; hospitalization for heart failure (HHF); HHF or CV death; all-cause mortality; a renal composite; and a combined renal and CV composite. Of 14,543 participants, 2113 had HF at baseline, and 1280 were on BB + RAASi. In those with a history of HF, participants on BB + RAASi therapy were more likely to have coronary atherosclerotic disease (82 vs 72%, p < 0.001), history of myocardial infarction (42 vs 29%, p < 0.001), higher mean body mass index (34 vs 32 kg/m2, p < 0.001), and lower mean estimated glomerular filtration rate (67 vs 70 mL/min/1.73 m2, p < 0.01). They were also more likely to be on insulin, a statin, antithrombotic agent, and a diuretic (all p < 0.001). In unadjusted analysis and when adjusted for selected baseline factors, there was no heterogeneity in canagliflozin treatment effect except for HHF/CV death in those on baseline BB + RAASi vs. those not on baseline BB + RAASi (Pheterogeneity = 0.02). Canagliflozin mostly improved CV and kidney outcomes in participants with a history of HF irrespective of use of BB + RAASi at baseline, with possible greater benefit on HHF/CV death in participants on BB + RAASi.


[Selective effect of p-aminobenzoic acid on mutagenesis: phenotypic analysis of the Arg+-revertants induced by N-nitroso-N-methylurea in the Escherichia coli K-12 AB1157 strain].
According to the phenotypic analysis of Arg+ revertants in Escherichia coli K-12 AB1157, the specific mutational changes in bacterial cells under the action of MNU were registered. True and suppressor mutations of four phenotypic groups were noted. The quantity of mutants induced depended upon the DNA and protein syntheses in bacterial cells. The sublethal concentration of para-aminobenzoic acid markedly (10-50 fold) reduced the rate of mutagenic induction and changed the quantity relations of mutants within phenotypic groups.


Evaluating students' perceptions of an interprofessional problem-based pilot learning project.
Interprofessional teams provide the promise of effective, comprehensive and reliable care. Interprofessional education (IPE) promotes students' knowledge and attitudes to support interprofessional teamwork, and problem-based learning formats enable students to gain valuable teamwork experience. To design, implement, and evaluate an interprofessional problem-based learning module in a large Canadian university focusing on the effects of this format on students' knowledge, attitudes, and perceptions. A pre-post mixed-methods research design was used, with a convenience sample of 24 students from medicine, pharmacy, nursing, physical therapy, and occupational therapy. Participants in the module were divided into 5 teams composed of one member from each discipline. Pre-tests were delivered just prior to module participation and post-tests directly followed. Students also participated in focus groups to provide feedback about module content, process, outcomes, and practical considerations. Students' attitudes toward interprofessional teamwork improved from baseline to post-intervention. Mean differences were significant using paired t-tests on confidence in professional role (p <0.001), communication (p = 0.02), understanding roles of others (p = 0.002), identification with the team (p = 0.002), comfort with members (p = 0.047), cooperation with team members (p = 0.004), team perceptions (p = 0.04), decision-making (p <0.001), team efficiency (p <0.001), minimal conflict (p = 0.04), and group contributions (p = 0.03). Focus group themes indicated students were satisfied with the module, perceived increased knowledge about roles and perspectives, greater confidence to collaborate, and increased motivation to engage in intra-curricular IPE. The timing of their exposure within their respective educational programs was identified as important.


Efficacy of sphenopalatine ganglion blockade in 66 patients suffering from cluster headache: a 12- to 70-month follow-up evaluation.
This study was conducted to evaluate the efficacy, based on 12- to 70-month follow-up data, of radiofrequency (RF) lesions of the sphenopalatine ganglion made in patients suffering from cluster headache. Sixty-six patients suffering from either episodic (Group A, 56 patients) or chronic (Group B, 10 patients) cluster headache who were not responsive to pharmacological management were treated by RF lesioning in the sphenopalatine ganglion. Complete relief of pain was achieved in 34 (60.7%) of 56 patients in Group A and in three (30%) of 10 patients in Group B. No relief was found in eight patients (14.3%) in Group A and in four (40%) in Group B. The mean time of follow up was 29.1 +/- 10.6 months in Group A and 24 +/- 9.7 months in Group B, ranging from 12 to 70 months. With regard to side effects and complications, temporary postoperative epistaxis was observed in eight patients and a cheek hematoma in 11 patients; a partial RF lesion of the maxillary nerve was inadvertently made in four patients. Nine patients complained of hypesthesia of the palate, which disappeared in all cases within 3 months. The authors conclude that RF lesioning in the sphenopalatine ganglion via the infrazygomatic approach may be performed in patients suffering from cluster headache that does not respond to pharmacological therapy.


Developmental Changes in Brain Network Hub Connectivity in Late Adolescence.
The human brain undergoes substantial development throughout adolescence and into early adulthood. This maturational process is thought to include the refinement of connectivity between putative connectivity hub regions of the brain, which collectively form a dense core that enhances the functional integration of anatomically distributed, and functionally specialized, neural systems. Here, we used longitudinal diffusion magnetic resonance imaging to characterize changes in connectivity between 80 cortical and subcortical anatomical regions over a 2 year period in 31 adolescents between the ages of 15 and 19 years. Connectome-wide analysis indicated that only a small subset of connections showed evidence of statistically significant developmental change over the study period, with 8% and 6% of connections demonstrating decreased and increased structural connectivity, respectively. Nonetheless, these connections linked 93% and 90% of the 80 regions, respectively, pointing to a selective, yet anatomically distributed pattern of developmental changes that involves most of the brain. Hub regions showed a distinct tendency to be highly connected to each other, indicating robust "rich-club" organization. Moreover, connectivity between hubs was disproportionately influenced by development, such that connectivity between subcortical hubs decreased over time, whereas frontal-subcortical and frontal-parietal hub-hub connectivity increased over time. These findings suggest that late adolescence is characterized by selective, yet significant remodeling of hub-hub connectivity, with the topological organization of hubs shifting emphasis from subcortical hubs in favor of an increasingly prominent role for frontal hub regions.


Action spectra of oxygen production and chlorophyll a fluorescence in the green microalga Nannochloropsis oculata.
The first complete action spectrum of oxygen evolution and chlorophyll a fluorescence was measured for the biofuel candidate alga Nannochloropsis oculata. A novel analytical procedure was used to generate a representative and reproducible action spectrum for microalgal cultures. The action spectrum was measured at 14 discrete wavelengths across the visible spectrum, at an equivalent photon flux density of 60 μmol photon sm(-2) s(-1). Blue light (∼ 414 nm) was absorbed more efficiently and directed to photosystem II more effectively than red light (∼ 679 nm) at light intensities below the photosaturation limit. Conversion of absorbed photons into photosynthetic oxygen evolution was maximised at 625 nm; however, this maximum is unstable since neighbouring wavelengths (646 nm) resulted in the lowest photosystem II operating efficiency. Identifying the wavelength-dependence of photosynthesis has clear implications to optimising growth efficiency and hence important economic implications to the algal biofuels and bioproducts industries.


Scedosporium apiospermum contact lens-related keratitis: a case report and literature review.
Scedosporium apiospermum (SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or immunocompetent hosts. The eye is rarely involved. Keratomycosis is usually caused by plant-related injuries. Here, we describe a patient with a severe and sight-threatening corneal abscess caused by SA, which was associated with contact lens wear and was successfully treated with a combination of surgical and medical therapies. An otherwise healthy 22-year-old woman, with history of contact lens wearing, was referred to the Ophthalmic Department of Bari University, Bari, Italy for evaluation of a corneal abscess and hypopyon in her left eye. Intensive topical and systemic antibiotic therapy was initiated after obtaining con- junctival swabs. Within 2 days, her ophthalmic condition had worsened, and her best-corrected visual acuity (BCVA) dropped to counting fingers. She underwent penetrating keratoplasty, after which her ophthalmic condition improved. Microbiological culture, obtained from the explanted cornea, revealed SA infection. This was addressed with specific topical and systemic therapy using voriconazole. Two weeks later, the con- dition of her left eye was stable, with mild corneal edema and no sign of acute graft rejection. Her BCVA improved to 20/25, and all medications were discontinued, except for the steroid eye drop. The patient was scheduled for a 1-month follow-up. Prompt identification of the etiological agent is mandatory to perform appropriate therapy in cases of keratomycosis. Surgery to remove the infected cornea is helpful in patients with deteriorating condition, in whom the initial medical therapy has failed. Topical and systemic antimycotic therapy, based on microbiological culture, is recommended as an adjunctive therapy for the surgical management of severe corneal mycotic abscesses.


Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.


Towards remote monitoring in pediatric care and clinical trials-Tolerability, repeatability and reference values of candidate digital endpoints derived from physical activity, heart rate and sleep in healthy children.
Digital devices and wearables allow for the measurement of a wide range of health-related parameters in a non-invasive manner, which may be particularly valuable in pediatrics. Incorporation of such parameters in clinical trials or care as digital endpoint could reduce the burden for children and their parents but requires clinical validation in the target population. This study aims to determine the tolerability, repeatability, and reference values of novel digital endpoints in healthy children. Apparently healthy children (n = 175, 46% male) aged 2-16 were included. Subjects were monitored for 21 days using a home-monitoring platform with several devices (smartwatch, spirometer, thermometer, blood pressure monitor, scales). Endpoints were analyzed with a mixed effects model, assessing variables that explained within- and between-subject variability. Endpoints based on physical activity, heart rate, and sleep-related parameters were included in the analysis. For physical-activity-related endpoints, a sample size needed to detect a 15% increase was calculated. Median compliance was 94%. Variability in each physical activity-related candidate endpoint was explained by age, sex, watch wear time, rain duration per day, average ambient temperature, and population density of the city of residence. Estimated sample sizes for candidate endpoints ranged from 33-110 per group. Daytime heart rate, nocturnal heart rate and sleep duration decreased as a function of age and were comparable to reference values published in the literature. Wearable- and portable devices are tolerable for pediatric subjects. The raw data, models and reference values presented here can be used to guide further validation and, in the future, clinical trial designs involving the included measures.


Role for yeast inhibitor of apoptosis (IAP)-like proteins in cell division.
Inhibitors of apoptosis (IAPs) are a family of proteins that bear baculoviral IAP repeats (BIRs) and regulate apoptosis in vertebrates and Drosophila melanogaster. The yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe both encode a single IAP, designated BIR1 and bir1, respectively, each of which bears two BIRs. In rich medium, BIR1 mutant S. cerevisiae underwent normal vegetative growth and mitosis. Under starvation conditions, however, BIR1 mutant diploids formed spores inefficiently, instead undergoing pseudohyphal differentiation. Most spores that did form failed to survive beyond two divisions after germination. bir1 mutant S. pombe spores also died in the early divisions after spore germination and became blocked at the metaphase/anaphase transition because of an inability to elongate their mitotic spindle. Rather than inhibiting caspase-mediated cell death, yeast IAP proteins have roles in cell division and appear to act in a similar way to the IAPs from Caenorhabditis elegans and the mammalian IAP Survivin.


Chromatographic Methods Developed for the Quantification of Quercetin Extracted from Natural Sources: Systematic Review of Published Studies from 2018 to 2022.
Quercetin (QUE) is the most widely used flavonoid for therapeutic purposes. To improve the available knowledge about the properties of some natural products, determining the amount of QUE is crucial. The main objective of this systematic review is to identify the analytical methods validated for detecting and quantifying QUE in different matrices and characterize their sensitivity. A search was conducted until 30 June 2023 in the PubMed database for experimental studies that addressed the validation of chromatographic analytical methods to detect and quantify QUE from consumable natural products. Only studies published between 2018 and 2022, written in English, were included. The risk of bias was assessed by emphasizing methods of comparison according to previously published studies. Descriptive statistics were used to depict the obtained results. The studies were analyzed based on the type of QUE source, chromatographic method, and validation parameters. A total of 17 studies were included in this review. Plants were the most commonly analyzed source of QUE. Among the detection methods, spectrophotometry proved to be the most widely used, surpassing mass spectrometry (MS). After analyzing the bias, all the included studies mentioned/presented, totally or partially, at least four of the eight parameters.


Occurrence, Distribution, and Trophic Transfer of Pharmaceuticals and Personal Care Products in the Bohai Sea.
The ubiquitous presence of pharmaceuticals and personal care products (PPCPs) in environments has aroused global concerns; however, minimal information is available regarding their multimedia distribution, bioaccumulation, and trophic transfer in marine environments. Herein, we analyzed 77 representative PPCPs in samples of surface and bottom seawater, surface sediments, and benthic biota from the Bohai Sea. PPCPs were pervasively detected in seawater, sediments, and benthic biota, with antioxidants being the most abundant PPCPs. PPCP concentrations positively correlated between the surface and bottom water with a decreasing trend from the coast to the central oceans. Higher PPCP concentrations in sediment were found in the Yellow River estuary, and the variations in the physicochemical properties of PPCPs and sediment produced a different distribution pattern of PPCPs in sediment from seawater. The log Dow, but not log Kow, showed a linear and positive relationship with bioaccumulation and trophic magnification factors and a parabolic relationship with biota-sediment accumulation factors. The trophodynamics of miconazole and acetophenone are reported for the first time. This study provides novel insights into the multimedia distribution and biomagnification potential of PPCPs and suggests that log Dow is a better indicator of their bioaccumulation and trophic magnification.


From mechanical to integrated organizations: the leader's challenge.
The leader in a nursing organization, whether it is the nurse manager or the nurse executive, is only as good as the positive synergistic relations that are developed with all parts of the organization. The converse is also true that the leader of any part of the organization is only as good as the synergistic relations she/he develops with the nurses and direct caregivers. Synchronicity is the mark of an effective organization and the hallmark of integrated organizations.


Modulator effect of mangiferin on biochemical characterization in 7,12-dimethylbenz[a]anthracene induced oral cancer in experimental hamsters.
Newly, chemo-preventive technique might be a hopeful advancement in developing countries for treating cancers with the aid of toxic less natural based constituents. Malignancy urges to augment effectual chemo-preventive agents that are look forward to suppress the tumours which may be stimulated by chewing and smoking of tobacco and over alcohol consumption related with the high prevalence of human oral cancer (OC) patients. In the present research, we examined to assess antioxidants, lipid peroxidation (LPO) and detoxification enzymes levels of anticancer activity of mangiferin on 0.5% 7.12-dimethylbenz[a]anthracene (DMBA) provoked hamster cheek pouch carcinoma (HCPC). OC on hamster buccal pouch (HBP) was incited by DMBA treatment for thrice per week for over 14 weeks. 100% well defined OC establishment with body weight (bw), tumour burden (TB), antioxidant, LPO and liver marker enzymes and also histological changes were observed on DMBA-challenged buccal pouch carcinoma (BPC) in hamsters. Orally treated mangiferin at an effective dosage of 50 mg/kg bw, to DMBA painted hamsters were significantly averted the body weight, succession of tumour, the biochemical as well as histopathological changes. Findings of this work clearly suggest that the anti-carcinoma effect of mangiferin possesses the modulator effects on potent antioxidant, anti-LPO and detoxification agents to expel the metabolites of malignant cells, on DMBA-provoked BPC in hamsters.


Intake of high levels of vitamin A and polyunsaturated fatty acids during different developmental periods modifies the expression of morphogenesis genes in European sea bass (Dicentrarchus labrax).
The effect of the feeding period on larval development was investigated in European sea bass larvae by considering the expression level of some genes involved in morphogenesis. Larvae were fed a control diet except during three different periods (period A: from 8 to 13 d post-hatching (dph); period B: from 13 to 18 dph; period C: from 18 to 23 dph) with two compound diets containing high levels of vitamin A or PUFA. European sea bass morphogenesis was affected by these two dietary nutrients during the early stages of development. The genes involved in morphogenesis could be modulated between 8 and 13 dph, and our results indicated that retinoids and fatty acids influenced two different molecular pathways that in turn implicated two different gene cascades, resulting in two different kinds of malformation. Hypervitaminosis A delayed development, reducing the number of vertebral segments and disturbing bone formation in the cephalic region. These malformations were correlated to an upregulation of retinoic acid receptor gamma, retinoid X receptor (RXR) alpha and bone morphogenetic protein (BMP)4. An excess of PUFA accelerated the osteoblast differentiation process through the upregulation of RXRalpha and BMP4, leading to a supernumerary vertebra. These results suggest that the composition of diets devoted to marine fish larvae has a particularly determining effect before 13 dph on the subsequent development of larvae and juvenile fish.


A chemical proteomics approach to identify c-di-GMP binding proteins in Pseudomonas aeruginosa.
In many bacteria, high levels of the ubiquitous second messenger c-di-GMP have been demonstrated to suppress motility and to promote the establishment of surface-adherent biofilm communities. While molecular mechanisms underlying the synthesis and degradation of c-di-GMP have been comprehensively characterized, little is known about how c-di-GMP mediates its regulatory effects. In this study, we have established a chemical proteomics approach to identify c-di-GMP interacting proteins in the opportunistic pathogen Pseudomonas aeruginosa. A functionalized c-di-GMP analog, 2'-aminohexylcarbamoyl-c-di-GMP (2'-AHC-c-di-GMP), was chemically synthesized and following its immobilization used to perform affinity pull down experiments. Enriched proteins were subsequently identified by high-resolution mass spectrometry. 2'-AHC-c-di-GMP was also employed in surface plasmon resonance studies to evaluate and quantify the interaction of c-di-GMP with its potential target molecules in vitro. The biochemical tools presented here may serve the identification of novel classes of c-di-GMP effectors and thus contribute to a better characterization and understanding of the complex c-di-GMP signaling network.


[Monovalent cation selectivity of EDTA-modified calcium channels].
Properties of slow inward sodium currents evoked by membrane depolarization in calcium-free EDTA-containing extracellular solution were studied on isolated intracellularly dialyzed neurons of the mollusc Helix pomatia. The relative permeability of the corresponding ionic channels determined from the shifts of the reversal potential was PNa+ :PLi+ :PNH2NH3+ :POHNH3+ = 1.00:0.80:0.55:0.21. For original sodium channels of the same membrane the relative values were 1.00:1.04:0.44:0.19. The induced sodium current could be blocked by calcium-channels blockers D-600 and niphedipine more effectively than calcium currents in the same membrane (the corresponding dissociation constants were 10(-5)M and 0.8 . 10(-5)M for the induced sodium current comparing with 2.6 . 10(-5)M and 2.3 . 10(-5)M for the calcium current. On the basis of these data a suggestion is made that the calcium channels possess a main selectivity filter which is similar to that of sodium channels, and an additional external binding site which binds divalent cations and prevents monovalent cations from entering the channel. Calcium-chelating agents introduced into calcium-free extracellular solution release this binding site from the occupying ion and thus transform the calcium channel into a sodium one.


The INDETERMINATE DOMAIN Protein BROAD LEAF1 Limits Barley Leaf Width by Restricting Lateral Proliferation.
Variation in the size, shape, and positioning of leaves as the major photosynthetic organs strongly impacts crop yield, and optimizing these aspects is a central aim of cereal breeding [1, 2]. Leaf growth in grasses is driven by cell proliferation and cell expansion in a basal growth zone [3]. Although several factors influencing final leaf size and shape have been identified from rice and maize [4-14], what limits grass leaf growth in the longitudinal or transverse directions during leaf development remains poorly understood. To identify factors involved in this process, we characterized the barley mutant broad leaf1 (blf1). Mutants form wider but slightly shorter leaves due to changes in the numbers of longitudinal cell files and of cells along the leaf length. These differences arise during primordia outgrowth because of more cell divisions in the width direction increasing the number of cell files. Positional cloning, analysis of independent alleles, and transgenic complementation confirm that BLF1 encodes a presumed transcriptional regulator of the INDETERMINATE DOMAIN family. In contrast to loss-of-function mutants, moderate overexpression of BLF1 decreases leaf width below wild-type levels. A functional BLF1-vYFP fusion protein expressed from the endogenous promoter shows a dynamic expression pattern in the shoot apical meristem and young leaf primordia. Thus, we propose that the BLF1 gene regulates barley leaf size by restricting cell proliferation in the leaf-width direction. Given the agronomic importance of canopy traits in cereals, identifying functionally different BLF1 alleles promises to allow for the generation of optimized cereal ideotypes.


Impact of an educational program on the feeding of neurologically impaired children.
To verify the impact of an educative program focused on aspects related to feeding developed with a group of caregivers of children with chronic non-progressive encephalopathy. Cross-sectional comparative study conducted with 30 children diagnosed with chronic non-progressive encephalopathy and their caregivers with the use of a questionnaire and video recordings of a meal conducted by the main caregiver. In order to verify the impact of an educational program in the knowledge and conduct of caregivers, patients were divided into two groups: study--consisting of caregivers submitted to a questionnaire and a video recording before and after the educational program; control--group in which caregivers underwent the procedures in two occasions, but without access to the educational program. Around 93.33% of caregivers were females, most had low educational level, and only 10% had a professional activity. Previous knowledge of caregivers concerning feeding was restricted, with 66% of caregivers not knowing what aspiration was, 60% being unfamiliar with the complications associated with such occurrence, and 86.66% stating that there is no relation between voice and swallowing. During feeding, only 26.66% of the caregivers used verbal commands related to feeding, and 50% did not realize the difficulties presented by their children. We observed a difference with regard to knowledge and conduct in the study group only. The educational program had a positive impact on the knowledge and conduct of caregivers concerning the feeding of their children with chronic non-progressive encephalopathy.


Uptake of phosphate by Synechocystis sp. PCC 6803 in dark conditions: Removal driving force and modeling.
Rapid uptake of inorganic phosphate (Pi) by microalgae should occur through two processes operating in parallel: onto extracellular polymeric substances (EPS) and intracellular polymeric substances (IPS). Most previous studies focused only on overall Pi uptake and ignored the roles of EPS. We investigated the two-step removal of Pi by Synechocystis sp. PCC 6803 in dark conditions (i.e., without incorporation of Pi into newly synthesized biomass). We also developed a model to simulate both steps. Experimental results with Synechocystis confirmed that Pi in the bulk solution was removed by the two uptake mechanisms operating in parallel, but with different kinetics. All uptake rates decreased with time, and the Pi uptake rate by IPS was much higher than that by EPS at all times, but EPS had a larger maximum Pi-storage capacity -- 33-48 mgP/gCODEPS versus 15-17 mgP/gCODIPS. Synechocystis had a maximum Pi-storage capacity in the range of 22-28 mgP/g dry biomass. Protein in EPS and IPS played the key role for binding Pi, and biomass with higher protein content had greater Pi-storage capacity. Furthermore, biomass with low initial stored Pi had faster Pi-uptake kinetics, leading to more Pi removed from the bulk solution. This work lays the foundation for using microalgae as a means to remove Pi from polluted water and for understanding competition for Pi in microbial communities.


Parents' worries about recurrent abdominal pain in children.
Recurrent abdominal pain is a common childhood disorder characterized by multiple episodes of stomachaches severe enough to interrupt daily activities. Recurrent abdominal pain is a difficult diagnosis for parents, children, and clinicians since there is no definitive cause of the symptoms. Research has shown recurrent abdominal pain is at least partly learned through social modeling. The purpose of this study was to understand parental worries and fears of recurrent abdominal pain that explain parental reinforcement of illness behavior. In-depth interviews were held with 15 parents of children diagnosed with recurrent abdominal pain. Parental cognitions were identified and thematically grouped. Two independent judges coded the interviews for the categories (88% inter-judge reliability). Six major categories of worries were identified. Parental cognitions about recurrent abdominal pain revolved around the fear of a disease and a desire for diagnosis and effective treatment. Many parents stated they felt helpless to know how to deal with their child's suffering. These fears and worries may explain why parents reinforce illness behavior by showing empathy for a supposedly sick child. The findings also identified areas of possible miscommunications between clinicians and parents. This study adds to our understanding of parents' view on recurrent abdominal pain and gives us tools to address cognitions that can perpetuate symptoms in children.


A prospective study comparing the quality of coronary computed tomography angiography images from photon counting and energy integrating detector systems.
As guidelines endorse the use of computed tomography (CT) for examining coronary artery disease (CAD), it is important to compare the advantages and disadvantages of the novel photon counting detector CT (PCD-CT) technology with the established energy integrating detector CT (EID-CT). To compare the image quality of coronary computed tomography angiography (CCTA) and the Agatston scores (AS) derived from EID-CT and PCD-CT. In this prospective observational study, 28 patients underwent clinical calcium score and CCTA scans on an EID-CT and a PCD-CT scanner. CCTA images were qualitatively analyzed by five observers using visual grading characteristics. The correlation and agreement of the AS were assessed using Spearman's rank correlation and Bland-Altman plots. This qualitative analyses demonstrated a high fraction of "good" or "excellent" ratings for the image criteria in both CT systems. The sharpness of the distal lumen and image quality regarding motion artifacts were rated significantly higher for EID-CT (P < 0.05). However, the sharpness of coronary calcification was rated significantly higher for PCD-CT (P < 0.05). Spearman's rank correlation and Bland-Altman plots showed good correlation (P = 0.95) and agreement regarding the AS between EID-CT and PCD-CT. Both CT systems exhibited high CCTA image quality. The sharpness of calcifications was rated significantly higher for PCD-CT. A good correlation was observed between the AS derived from the two systems.


Drosophila TRP channels.
The transient receptor potential (TRP) superfamily comprises a large group of related cation channels that display surprising diversity in the specific modes of activation and cation selectivities. However, a unifying theme is that many TRP channels play important roles in sensory physiology. The superfamily includes 28 mammalian members, which are subdivided into multiple subfamilies. Each of these subfamilies is represented by at least one of the 13 members in Drosophila, suggesting common evolutionary relationships. In recent years it has become clear that TRP channels in flies and mammals participate in similar sensory modalities. These include, but are not limited to, hearing, thermosensation, and certain specialized types of vision. With the recent flurry of new studies, 9 out of the 13 TRPs have been addressed in various contexts. As a result, the repertoire of biological roles attributed to Drosophila TRPs has increased considerably and is likely to lead to many additional surprises over the next few years.


Post-spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG.
OBJECTIVE The most actively explored therapeutic strategy for overcoming spinal cord injury (SCI) is the delivery of genes encoding molecules that stimulate regeneration. In a mouse model of amyotrophic lateral sclerosis and in preliminary clinical trials in patients with amyotrophic lateral sclerosis, the combined administration of recombinant adenoviral vectors (Ad5-VEGF+Ad5-ANG) encoding the neurotrophic/angiogenic factors vascular endothelial growth factor ( VEGF) and angiogenin ( ANG) was found to slow the development of neurological deficits. These results suggest that there may be positive effects of this combination of genes in posttraumatic spinal cord regeneration. The objective of the present study was to determine the effects of Ad5-VEGF+Ad5-ANG combination therapy on motor function recovery and reactivity of astrocytes in a rat model of SCI. METHODS Spinal cord injury was induced in adult Wistar rats by the weight-drop method. Rats (n = 51) were divided into 2 groups: the experimental group (Ad5-VEGF+Ad5-ANG) and the control group (Ad5-GFP [green fluorescent protein]). Recovery of motor function was assessed using the Basso, Beattie, and Bresnahan scale. The duration and intensity of infectivity and gene expression from the injected vectors were assessed by immunofluorescent detection of GFP. Reactivity of glial cells was assessed by changes in the number of immunopositive cells expressing glial fibrillary acidic protein (GFAP), S100β, aquaporin 4 (AQP4), oligodendrocyte transcription factor 2, and chondroitin sulfate proteoglycan 4. The level of S100β mRNA expression in the spinal cord was estimated by real-time polymerase chain reaction. RESULTS Partial recovery of motor function was observed 30 days after surgery in both groups. However, Basso, Beattie, and Bresnahan scores were 35.9% higher in the Ad5-VEGF+Ad5-ANG group compared with the control group. Specific GFP signal was observed at distances of up to 5 mm in the rostral and caudal directions from the points of injection. A 1.5 to 2.0-fold increase in the number of GFAP+, S100β+, and AQP4+ cells was observed in the white and gray matter at a distance of up to 5 mm from the center of the lesion site in the caudal and rostral directions. At 30 days after injury, a 2-fold increase in S100β transcripts was observed in the Ad5-VEGF+Ad5-ANG group compared with the control group. CONCLUSIONS Intraspinal injection of recombinant adenoviral vectors encoding VEGF and ANG stimulates functional recovery after traumatic SCI. The increased number of S100β+ astrocytes induced by this approach may be a beneficial factor for maintaining the survival and function of neurons. Therefore, gene therapy with Ad5-VEGF+Ad5-ANG vectors is an effective therapeutic method for SCI treatment.