The ASAS Health Index and Environmental Factors Item Set: validity and reliability of the Swedish translations in Swedish patients with ankylosing spondylitis.

OBJECTIVES: To translate the Assessment of SpondyloArthritis international Society (ASAS) Health Index (HI) Environmental Factors Item Set (EFIS) into Swedish and culturally adapt it for a Swedish context, and to assess the construct validity of the Swedish version of the ASAS HI and test-retest reliability in ASAS HI and EFIS in Swedish patients with ankylosing spondylitis (AS). METHOD: Translation and cross-cultural adaptation of the EFIS were carried out according to a forward-backward procedure consisting of five steps. The construct validity of the ASAS HI was tested using Spearman correlation with standard health outcomes for axial spondyloarthritis (axSpA). Reliability was analysed by internal consistency with the Cronbach's alpha coefficient for ASAS HI, and test-retest reliability with intraclass correlation coefficients (ICCs) for ASAS HI and kappa agreement for the individual items of EFIS. RESULTS: The translation of EFIS showed acceptable face and content validity. ASAS HI showed an acceptable internal consistency (Cronbach's alpha 0.79), and excellent test-retest reliability (ICC 0.87). Test-retest reliability for EFIS showed varied results, with kappa agreement for the individual items ranging from poor (-0.027) to good (0.80). CONCLUSIONS: The Swedish version of ASAS HI proved to be valid and reliable and is recommended for assessing the impact of AS on global functioning and health. A Swedish version of EFIS has been produced and uploaded on the ASAS website. The EFIS proved to have acceptable face and content validity, and may contribute to the contextual interpretation of the ASAS HI.

Wave propagation and focusing of soft X-rays by spherical bent microchannel plates.

Synchrotron radiation sources have been used to study the focusing properties and angular distribution of X-ray radiation at the exit of spherically bent microchannel plates (MCPs). In this contribution it is shown how soft X-ray radiation at energies up to 1.5 keV can be focused by spherically bent MCPs with curvature radii R of 30 mm and 50 mm. For these devices, a focus spot is detectable at a distance between the detector and the MCP of less than R/2, with a maximum focusing efficiency up to 23% of the flux illuminating the MCP. The soft X-ray radiation collected at the exit of microchannels of spherically bent MCPs are analyzed in the framework of a wave approximation. A theoretical model for the wave propagation of radiation through MCPs has been successfully introduced to explain the experimental results. Experimental data and simulations of propagating radiation represent a clear confirmation of the wave channeling phenomenon for the radiation in spherically bent MCPs.

Coincident angle-resolved state-selective photoelectron spectroscopy of acetylene molecules: a candidate system for time-resolved dynamics.

The acetylene-vinylidene system serves as a benchmark for investigations of ultrafast dynamical processes where the coupling of the electronic and nuclear degrees of freedom provides a fertile playground to explore the femto- and sub-femto-second physics with coherent extreme-ultraviolet (EUV) photon sources both on the table-top as well as free-electron lasers. We focus on detailed investigations of this molecular system in the photon energy range 19-40 eV where EUV pulses can probe the dynamics effectively. We employ photoelectron-photoion coincidence (PEPICO) spectroscopy to uncover hitherto unrevealed aspects of this system. In this work, the role of excited states of the C2H2+ cation, the primary photoion, is specifically addressed. From photoelectron energy spectra and angular distributions, the nature of the dissociation and isomerization channels is discerned. Exploiting the 4π-collection geometry of the velocity map imaging spectrometer, we not only probe pathways where the efficiency of photoionization is inherently high but also perform PEPICO spectroscopy on relatively weak channels.

Penning spectroscopy and structure of acetylene oligomers in He nanodroplets.

Embedded atoms or molecules in a photoexcited He nanodroplet are well-known to be ionized through inter-atomic relaxation in a Penning process. In this work, we investigate the Penning ionization of acetylene oligomers occurring from the photoexcitation bands of He nanodroplets. In close analogy to conventional Penning electron spectroscopy by thermal atomic collisions, the n = 2 photoexcitation band plays the role of the metastable atomic 1s2s 3,1S He*. This facilitates electron spectroscopy of acetylene aggregates in the sub-Kelvin He environment, providing the following insight into their structure: the molecules in the dopant cluster are loosely bound van der Waals complexes rather than forming covalent compounds. In addition, this work reveals a Penning process stemming from the n = 4 band where charge-transfer from autoionized He in the droplets is known to be the dominant relaxation channel. This allows for excited states of the remnant dopant oligomer Penning-ions to be studied. Hence, we demonstrate Penning ionization electron spectroscopy of doped droplets as an effective technique for investigating dopant oligomers which are easily formed by attachment to the host cluster.

Preliminary evidence that vortioxetine may improve sleep quality in depressed patients with insomnia: a retrospective questionnaire analysis.

Insomnia is a frequent symptom in depressed patients. It can present with difficulty in initiating and/or maintaining sleep. We retrospectively evaluated a group of 15 patients affected by major depressive disorder and complaining of insomnia, who started vortioxetine (VOR) treatment for their depressive symptoms. The following questionnaires were captured at baseline and follow-up: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Beck Depression Inventory. Pittsburgh Sleep Quality Index total score significantly decreased between follow-up and baseline (P < 0.01), and in several subitems related to sleep quality and continuity. Moreover, Epworth Sleepiness Scale decreased between follow-up and baseline (P < 0.01). Finally, Beck Depression Inventory reduction was also evident between follow-up and baseline (P < 0.01). This retrospective analysis showing the significant effect of VOR on both depressive symptoms and insomnia in patients showing comorbid major depressive disorder and insomnia invites further research in order to confirm this preliminary evidence. We hypothesize that the VOR mechanism of action may explain the improvement of subjective sleep, other than depressive symptoms.

The etiology of low-grade gliomas: pathological and clinical considerations about radiation-induced low-grade gliomas.

The only environmental factor undoubtedly linked to an increased risk of brain tumors (including gliomas) is therapeutic X-rays. We aim to conduct a detailed study of radiation-induced low-grade gliomas, in order to better understand the pathogenesis of such gliomas. Furthermore, we want do prove whether or not there are significant differences, according to clinical features and biological behavior, between this type of tumor and general low-grade gliomas. We analyzed the existent literature of low-grade radiation-induced glioma case reports and other epidemiological reports based on the experience of the senior author. We were able to collect 20 cases of such gliomas. Demographic data and previous X-ray details, along with latency intervals of all patients are provided. The amount of radiation able to cause mutations is not necessarily very high, as tumors occur even after low doses of radiation (as 3-5 GY). The incidence of this kind of tumors may be underestimated and may rise in the future. Care must be taken when observing patients who were irradiated more than 10 years before, especially in the recent years in which access to radiosurgical and radiation therapies has increased in the general population for treating many cerebral pathologies. Radiation-induced low-grade gliomas appear to be different from general gliomas only in terms of age in which they occur. In terms of clinical and biological behavior, there seem to be no differences, even though exceptional cases are reported.

Single brain metastases from cervical carcinoma: report of two cases and critical review of the literature.

Single brain metastases from cervical carcinomas are rare. We report two cases of solitary brain metastases, showing different histological types, which have been excised with microsurgical technique. Neuroendocrine differentiation does not seem to be connected to clinical behavior, indeed a poor prognosis depends on poorly differentiated histological types. In our cases, brain metastases were a late event and they have been successfully excised in microsurgery, thanks to their solitary and resectable nature, and a well-controlled primary disease.

Four-year clinical and neuroradiological follow-up of a papillary tumor of the pineal region.

Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years' clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.

Predictors of germline status for hereditary melanoma: 5 years of multi-gene panel testing within the Italian Melanoma Intergroup.

BACKGROUND: The incidence of cutaneous melanoma is increasing in Italy, in parallel with the implementation of gene panels. Therefore, a revision of national genetic assessment criteria for hereditary melanoma may be needed. The aim of this study was to identify predictors of susceptibility variants in the largest prospective cohort of Italian high-risk melanoma cases studied to date. MATERIALS AND METHODS: From 25 Italian centers, we recruited 1044 family members and germline sequenced 940 cutaneous melanoma index cases through a shared gene panel, which included the following genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP, MITF and ATM. We assessed detection rate according to familial status, region of origin, number of melanomas and presence and type of non-melanoma tumors. RESULTS: The overall detection rate was 9.47% (5.53% analyzing CDKN2A alone), ranging from 5.14% in sporadic multiple melanoma cases (spoMPM) with two cutaneous melanomas to 13.9% in familial cases with at least three affected members. Three or more cutaneous melanomas in spoMPM cases, pancreatic cancer and region of origin predicted germline status [odds ratio (OR) = 3.23, 3.15, 2.43, P < 0.05]. Conversely, age > 60 years was a negative independent predictor (OR = 0.13, P = 0.008), and was the age category with the lowest detection rate, especially for CDKN2A. Detection rate was 19% when cutaneous melanoma and pancreatic cancer clustered together. CONCLUSIONS: Gene panel doubled the detection rate given by CDKN2A alone. National genetic testing criteria may need a revision, especially regarding age cut-off (60) in the absence of strong family history, pancreatic cancer and/or a high number of cutaneous melanomas.

Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide.

Epigenetic silencing of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene by promoter methylation is correlated with improved progression-free survival (PFS) and overall survival (OS) in adult patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this study is to determine the correlation between MGMT and survival in elderly patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty-three patients aged 70 years or older with histologically confirmed GBM treated with RT plus TMZ between February 2005 and September 2009 were investigated in this study. The methylation status of the MGMT promoter was determined by polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months, respectively. The MGMT promoter was methylated in 42 patients (50.6%) and unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was 10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P = 0.0001). On multivariate analysis MGMT methylation status emerged as the strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ.

Safety and feasibility of the adjunct of local chemotherapy with biodegradable carmustine (BCNU) wafers to the standard multimodal approach to high grade gliomas at first diagnosis.

AIM: Among physicians there is still a reluctant attitude in the employment of combined treatment with surgery and intraoperative placement of carmustina 7.7 mg wafers (Gliadel®), followed by standard adjuvant treatment with radiotherapy and concomitant and subsequent chemiotherapy with temozolomide (TMZ), for supratentorial high grade gliomas at first diagnosis. To determine the safety and feasibility of this multimodality sequential adjuvant therapy, we reviewed our single-institution experience, in the light to provide more insights on this continuous multi-stage chemotherapy approach to such a challenging disease as glioblastoma multiforme. METHODS: From February 2006 to January 2008, 32 patients were treated at our institution for cerebral supratentorial high grade glioma with surgery and intraoperative placement of carmustine wafers. No postsurgical complications could be observed. After a median time of 4,8 weeks all patients began adjuvant concomitant radiotherapy with a mean of 60 Gy and TMZ chemotherapy 75 mg/m2 during which weekly hematologic assessments were performed. After 3 to 6 weeks patients commenced adjuvant TMZ, administered 5 days every 28, 200 mg/m2 for not less than 12 cycles. A contrast-enhanced magnetic resonance imaging (MRI) was routinely performed. Median follow-up after surgery was of 6.5 months, ranging from 4 to 23 months. RESULTS: The mean presurgical KPS was of 80 (range: from 60 to 100), and it remained unmodified after adjuvant therapies even at suspension of steroids. In 4 cases there was a radiologic evidence of progression of the disease and the necessity of steroids, with a progression-free survival (PFS) of 6, 8, 9,5 and 13,6 months. One case died 14 months after first operation. All other patients are still alive. CONCLUSION: The integration of local chemiotherapy with carmustine wafers and the standard adjuvant regimen with radiotherapy and concomitant chemiotherapy appears to be safe and feasible, without any adjunctive complication. Promising results on the efficacy require more follow up to be quantified.

Sarcoma metastatic to the brain: a series of 35 cases and considerations from 27 years of experience.

The authors report their 27-year experience regarding 35 cases of supratentorial brain metastasis from sarcoma treated in a single institution: these included ten osteosarcomas, seven leiomyosarcomas, five Ewing sarcomas, four malignant fibrous histiocytomas, three alveolar soft-part sarcomas (ASPS), two rhabdomyosarcomas, one liposarcoma, and three unclassified sarcomas. The first 15 cases of the series have already been described in a previous publication. Median survival after craniotomy was 9.8 months (range: 4-24). In patients with preoperative Karnofsky performance score (KPS) > 60 it was 12.8 months (range: 6.5-24 months) versus 5.4 months for those patients with a KPS < or = 60 (P = 0.01). Eight patients had more than one lesion, six of which were treated in the last ten years. Of the three patients with ASPS, the first two were alive at 15 and 20 months (before being lost to follow-up) whereas the third patient is alive at 24 month follow-up. The authors conclude that surgery is more effective in treating selected patients with sarcoma metastatic to the brain, and that patients with metastasis from ASPS have good prognosis when submitted to surgical treatment. The complete removal of all brain metastases "en bloc" and a KPS > 60 are associated with the best prognosis. Finally, it seems that surgical indications for multiple brain metastases from sarcoma have increased during the last ten years.

Electrophoretic deposition of polymethylmethacrylate and composites for biomedical applications.

For the first time, an electrophoretic deposition (EPD) method has been developed for the deposition of polymethylmethacrylate (PMMA) and PMMA-alumina films for biomedical implant applications. The proposed biomimetic approach was based on the use of a bile salt, sodium cholate (NaCh), which served as a multifunctional solubilizing, charging, dispersing and film-forming agent. Investigations revealed PMMA-Ch- and PMMA-alumina interactions, which facilitated the deposition of PMMA and PMMA-alumina films. This approach allows for the use of a non-toxic water-ethanol solvent for PMMA. The proposed deposition strategy can also be used for co-deposition of PMMA with other functional materials. The PMMA and composite films were tested for biomedical implant applications. The PMMA-alumina films showed statistically improved metabolic results compared to both the bare stainless steel substrate and pure PMMA films. Alkaline phosphatase (ALP) activity affirmed the bioactivity and osteoconductive potential of PMMA and composite films. PMMA-alumina films showed greater ALP activity than both the PMMA-coated and uncoated stainless steel.

Overall impact of speed-related initiatives and factors on crash outcomes.

From December 2000 until July 2002 a package of speed-related initiatives and factors took place in Victoria, Australia. The broad aim of this study was to evaluate the overall impact of the package on crash outcomes. Monthly crash counts and injury severity proportions were assessed using Poisson and logistic regression models respectively. The model measured the overall effect of the package after adjusting as far as possible for non-speed road safety initiatives and socio-economic factors. The speed-related package was associated with statistically significant estimated reductions in casualty crashes and suggested reductions in injury severity with trends towards increased reductions over time. From December 2000 until July 2002, three new speed enforcement initiatives were implemented in Victoria, Australia. These initiatives were introduced in stages and involved the following key components: More covert operations of mobile speed cameras, including flash-less operations; 50% increase in speed camera operating hours; and lowering of cameras' speed detection threshold. In addition, during the period 2001 to 2002, the 50 km/h General Urban Speed Limit (GUSL) was introduced (January 2001), there was an increase in speed-related advertising including the "Wipe Off 5" campaign, media announcements were made related to the above enforcement initiatives and there was a speeding penalty restructure. The above elements combine to make up a package of speed-related initiatives and factors. The package represents a broad, long term program by Victorian government agencies to reduce speed based on three linked strategies: more intensive Police enforcement of speed limits to deter potential offenders, i.e. the three new speed enforcement initiatives just described - supported by higher penalties; a reduction in the speed limit on local streets throughout Victoria from 60 km/h to 50 km/h; and provision of information using the mass media (television, radio and billboard) to reinforce the benefits of reducing low level speeding - the central message of "Wipe Off 5". These strategies were implemented across the entire state of Victoria with the intention of covering as many road users as possible. This study aimed to evaluate the overall effectiveness of the speed-related package. The study objectives were: to document the increased speed camera activity in each speed limit zone and in Melbourne compared with the rest of Victoria; to evaluate the overall effect on crash outcomes of the package; to account as far as possible for the effect on crash outcomes of non-speed road safety initiatives and socio-economic factors, which would otherwise influence the speed-related package evaluation; and to examine speed trends in Melbourne and on Victorian rural highways, especially the proportions of vehicles travelling at excessive speeds. This paper presents the results of the evaluation of the overall impact on crash outcomes associated with the speed-related package, after adjusting as far as possible for the effect of non-speed road safety initiatives and socio-economic factors. D'Elia, Newstead and Cameron (2007) document the study results in full.

Expression and function of the homeodomain-containing protein Hex in thyroid cells.

The homeodomain-containing protein Hex (also named Prh) is expressed in primitive endoderm (during the early phases of development), in some endoderm-derived tissues and in endothelial and hematopoietic precursors. Hex expression is exting-uished during terminal differentiation of endothelial and hematopoietic cells as well as in adult lung. Previous investigations have demonstrated that Hex is expressed during early thyroid gland development. No information has been reported on Hex expression in adult thyroid gland or on the function of this protein in follicular thyroid cells. These issues represent the focus of the present study. We demonstrate that Hex mRNA is present in rat and human adult thyroid gland as well as in differentiated follicular thyroid cell lines. In FRTL-5 cells TSH reduces Hex expression. In thyroid cell lines transformed by several oncogenes Hex expression is completely abolished. By using co-transfection assays we demonstrate that Hex is a repressor of the thyroglobulin promoter and that it is able to abolish the activating effects of both TTF-1 and Pax8. These data would suggest that Hex may play an important role in thyroid cell differentiation. Protein-DNA interaction experiments indicate that Hex is able to bind sites of the thyroglobulin promoter containing either the core sequence 5'-TAAT-3' or 5'-CAAG-3'. The DNA binding specificity of the Hex homeodomain, therefore, is more 'relaxed' than that observed in the majority of other homeo-domains.

Vibroacoustic stimulation in normal term human pregnancy.

OBJECTIVE: To examine the effects of vibroacoustic stimulation (VAS) on fetal heart rate (FHR) in term human fetuses by computerized carditocography system. METHODS: FHR was analyzed 20 min before and 30 min after vibroacoustic stimulation using the Oxford Sonicaid System 8002 for computerized FHR measurement. Recordings were made in 31 uncomplicated pregnancies at 36-42 weeks' gestation. RESULTS: Vibroacustic stimulation of the fetus evoked a significant increase in all the parameters evaluated (number of fetal movements, of accelerations above 10 and 15 bpm, in high- and low-variability episodes, and in short-term variations). Concerning the effect of behavioural states on the response to VAS, some changes (FHR, high-variability episodes) occurred independently of behavioural states, while other parameters (accelerations >10 and 15 bpm: short-term variation) underwent statistically significant changes only for behavioural states 1F and 2F. CONCLUSIONS: Our study supports the hypothesis of a significant fetal response in normal term pregnancy, as clearly shown by computerized cardiotocography. The immediate response occurred independently of behavioural states, although some differences were present (mainly for F1 and F2 states) if the evaluation was extended in time.

Genetic thrombophilias and uterine artery Doppler velocimetry and preeclampsia.

OBJECTIVE: The aim of this study was to evaluate the correlation between genetic thrombophilic mutations, uterine artery Doppler at 24 weeks of gestation and preeclampsia. METHODS: In a case control study we performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 20 weeks at our Department. RESULTS: The frequency of heterozygous carriers of the factor V Leiden was 17.4% in the women with preeclampsia and abnormal artery Doppler compared with 3.12% in the patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of prothrombin gene was 1.5 vs. 4.3% between women with normal pregnancies and with preeclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among the patients with preeclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic gene variants were found in women with preeclampsia and normal uterine artery Doppler. CONCLUSION: We demonstrated the important association between factor V Leiden mutation, abnormal uterine Doppler at 24 weeks and preeclampsia in our population.

Topical application of LEVORAG® as first-line treatment for chronic anal fissures: a preliminary multicentric study.

AIM: The aim of the present study was to assess the safety and efficacy of this new topical agent as a first line treatment in patients with chronic anal fissures. METHODS: Nine centres were involved in the study. Patients with chronic anal fissures were recruited and received Levorag® for 40 days. Follow-up visits were conducted at 10, 20 and 40 days from the recruitment. Primary outcome was the healing rate, secondary outcome the reduction of pain at the end of the treatment measured with a VAS scale. RESULTS: Fifty patients completed the treatment. No adverse events were recorded. 60% of patients healed completely at the end of the treatment. In those that did not heal the reduction of mean VAS values was 60%. CONCLUSION: The use of Levorag® on patients affected by chronic anal fissures achieved in the short term results similar to those experienced by more classic local treatments without any side effect.

Missense mutations of human homeoboxes: A review.

The homeodomain (encoded by the homeobox) is the DNA-binding domain of a large variety of transcriptional regulators involved in controlling cell fate decisions and development. Mutations of homeobox-containing genes cause several diseases in humans. A variety of missense mutations giving rise to human diseases have been described. These mutations are an excellent model to better understand homeodomain molecular functions. To this end, homeobox missense mutations giving rise to human diseases are reviewed. Seventy-four independent homeobox mutations have been observed in 17 different genes. In the same genes, 30 missense mutations outside the homeobox have been observed, indicating that the homeodomain is more easily affected by single amino acids changes than the rest of the protein. Most missense mutations have dominant effects. Several data indicate that dominance is mostly due to haploinsufficiency. Among proteins having the homeodomain as the only DNA-binding domain, three "hot spot" regions can be delineated: 1) at codon encoding for Arg5; 2) at codon encoding for Arg31; and 3) at codons encoding for amino acids of recognition helix. In the latter, mutations at codons encoding for Arg residues at positions 52 and 53 are prevalent. In the recognition helix, Arg residues at positions 52 and 53 establish contacts with phosphates in the DNA backbone. Missense mutations of amino acids that contribute to sequence discrimination (such as those at positions 50 and 54) are present only in a minority of cases. Similar data have been obtained when missense mutations of proteins possessing an additional DNA-binding domain have been analyzed. The only exception is observed in the POU1F1 (PIT1) homeodomain, in which Arg58 is a "hot spot" for mutations, but is not involved in DNA recognition.