KPNA2 predicts long term survival in patients with anaplastic oligoastrocytomas

The family of karyopherins comprises importins and exportins which are both involved in nucleocytoplasmic shuttling. Increased levels of karyopherin a2/importin 1 (KPNA2) and chromosome region maintenance protein 1/exportin 1 (CRM1) have been associated with poorer prognosis in patients with infiltrative astrocytomas. Isocitrate dehydrogenase 1 gene (IDH1) R132H mutation status was also recently identified as a prognostic factor for malignant gliomas. We evaluated KPNA2 and CRM1, as well as the IDH1 mutation status, as possible novel biomarkers for World Health Organization grade III anaplastic oligoastrocytomas (AOA). We analyzed nuclear expression of KPNA2 by immunohistochemistry in 72 primary anaplastic gliomas (29 AOA, 24 anaplastic astrocytomas, 19 anaplastic oligodendrogliomas). The IDH1 mutation status was also determined in patients with anaplastic astrocytomas and AOA, and AOA patients were additionally evaluated for CRM1 nuclear expression. Long term survivors (LTS; >8 years) with AOA showed lower KPNA2 expression levels compared to non-LTS (p = 0.005). KPNA2 expression (⩾5% versus <5%, 1–<5%, median) was found to correlate inversely with overall survival (OS) and progression-free survival (PFS) in our overall series as well as in the AOA group (anaplastic gliomas: OS p = 0.017; PFS p = 0.033; AOA: OS p = 0.017, PFS p = 0.040). Mutant IDH1-R132H was detected in 69% of the AOA cohort; a combination of KPNA2 low expression and mutant IDH1-R132H was only seen in LTS (p = 0.050). No differences between the histological subtypes were observed in terms of KPNA2 expression and IDH1-R132H mutation status. To our knowledge this is the first time it has been shown that KPNA2 expression may have potential as a prognostic biomarker for AOA as well.     

Missing data due to a 'checklist misconception-effect'

Summary. Objectives: To analyze the extent and relevance of a postulated “checklist misconception-effect” (a specific response pattern characterized by symptom-free persons not checking the “not at all”-category). Methods: Our data is derived from a survey of blue collar workers (n = 228) who previously had filed in applications for medical rehabilitation benefits. We defined the “checklist misconception-effect” by the following response pattern: (1) at least one missing value and (2) at least one valid item response and (3) no ‘not at all’ responses. Results: 75% of the responders had complete data, 16.2% a postulated ‘checklist misconception-effect’. Substantial covariations with socio-demographic characteristics or health status indicators could not be found. Additional imputation of missing values under the assumption of a “checklist misconception-effect” led to a reduction of missing data in the somatisation-subscale score from 12.3% to 0.4% compared to a simple manual-based calculation. Correlation with various external criteria (general health perception, level of functioning, depression) remained unchanged. Conclusions: Ignoring the “checklist misconception-effect” would overestimate symptom load. However, the validity of this effect has still to be proven in methodological studies.

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Zusammenfassung. Fehlende Werte durch den ‘Listenfragen-Fehldeutungseffekt’ Fragestellung: Item non-response kann die Gültigkeit von Studienergebnissen erheblich beeintr?chtigen. Am Beispiel der Subskala Somatisierung der SCL-90-R postulieren wir ein Antwortmuster (‘Listenfragen- Fehldeutungseffekt’), bei dem die Probanden bei Beschwerdefreiheit statt der vorgesehenen ‘überhaupt nicht’-Kategorie keine Antwort markieren. Die vorliegende Studie analysiert Ausma? und Bedeutung dieses ‘Listenfragen-Fehldeutungseffekts’. Methoden: Als Analysegrundlage dient eine postalische Befragung von n = 228 Versichterten einer Arbeiterrentenversicherung mit Antrag auf medizinische Rehabilitation. Der ‘Listenfragen- Fehldeutungseffekt’ wurde operationalisiert durch Antwortmuster (1) mit mindestens einem fehlenden Wert und (2) mindestens einem gültigen Wert und (3) Fehlen von ‘überhaupt nicht’-Antworten. Ergebnisse: 75% der Befragten hatten komplette Daten, 16,2% einen postulierten ‘Listenfragen-Fehldeutungseffekt’. Substanzielle Kovariationen mit soziodemografischen Merkmalen und Gesundheitsindikatoren wurden nicht gefunden. Durch zus?tzliche Imputation der fehlenden Werte unter der Annahme des ‘Listenfragen-Fehldeutungseffekts’ reduzierte sich der Anteil fehlender Skalenwerte im Vergleich zur einfachen Manual-gestützen Vorgehensweise von 12,3% auf 0,4%. Korrelationen mit verschiedenen Au?enkriterien (Gesundheitszustand, Funktionsf?higkeit, Depressivit?t) blieben konstant. Schlussfolgerungen: Die Nicht-Berücksichtigung des ‘Listenfragen-Fehldeutungseffekts’ führt zu einer übersch?tzung der Symptomauspr?gung. Die Gültigkeit des Effekts muss in weiteren methodischen Studien überprüft werden.

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Résumé. Non-réponses dues à une mauvaise conception du questionnaire Objectifs: Analyser l’importance d’un “checklist misconception-effect” (type de réponses dans lequel le sujet sans sympt?mes ne coche pas de réponse au lieu de cocher la réponse ?pas du tout?). Méthodes: Les données sont tirées d’une enquête par questionnaire postal auprès d’assurés (n = 228) d’une caisse de retraite ayant présenté un dossier pour un traitement de réadaptation. Le type de réponse dont il a été tenu compte pour identifier le “checklist misconception-effect” a été défini comme présentant (1) au moins une réponse manquante, (2) au moins une réponse valable (3), et aucune réponse ?pas du tout?. Résultats: 75% des personnes interrogées ont répondu à toutes les questions; chez 16,2% des personnes on a pu suspecter un “checklist misconception-effect”. Nous n’avons pas trouvé de covariations substantielles avec des aspects sociodémographiques ou des indicateurs de santé. Partant de l’hypothèse que ce “checklist misconception-effect” existe, les valeurs manquantes peuvent être remplacées et le nombre de réponses manquantes diminue par rapport au procédé conventionnel de 12,3% à 0,4%. Les corrélations avec divers critères (état de santé, vitalité, tendance dépressive) restent alors constantes. Conclusions: En ne tenant pas compte de ce “checklist misconception-effect” on induit une surestimation de l’intensité des sympt?mes. La validité de cet effet reste à vérifier par d’autres études.

     

NF-kappaB and inflammation in genetic disease

By responding to pro-inflammatory cytokines, such as IL-1beta and TNF-alpha, and controlling itself the expression of numerous mediators of inflammation, NF-kappaB plays a pivotal role in controlling the proper sequence of events characterizing the inflammation process. Although excessive NF-kappaB activation is often associated with inflammatory signs in many different tissues, impaired NF-kappaB activation can also generate inflammation. This is the case in humans suffering from the genetic disease incontinentia pigmenti that exhibit severe skin inflammation. Identifying the molecular basis of this pathology, mutations affecting the gene coding for NEMO, has allowed production of mouse models for investigating the disease. Their characterization supports the view that a very tight positive and negative regulation of the NF-kappaB signaling pathway is required in vivo to ensure not only a fine-tuned response to injury or infection but also to maintain tissue homeostasis.     

The psychological impact of external fixation using the Ilizarov or Orthofix LRS method to treat tibial osteomyelitis with a bone defect

ObjectiveTo examine the psychological impact of external fixation for a tibial bone defect due to osteomyelitis, and to compare the Orthofix limb reconstruction system (LRS) with the Ilizarov external fixator.Materials and methodsThe SCL-90-R questionnaire was administered at four different time points (before surgery, while patients wore the external fixation device, when the device was removed, and two to three months after). The scores at the four time points were compared, as were the two different methods of external fixation (Orthofix LRS vs. Ilizarov).ResultsThe patients experienced a significant adverse impact on their mental health, with the worst outcomes at Time 2 (while wearing the external fixator), but with some negative effects still present even several months after removal of the fixation device. Although the Orthofix LRS and Ilizarov groups showed similar mental health scores at Time 1 (preoperatively) and Time 3 (upon removal of the fixation device), the Orthofix LRS was associated with better scores, specifically in the Hostility (Time 2), Phobic Anxiety (Time 2), Psychoticism (Times 2 and 4), and Other (Time 2) sub-scores, as well as the total score (Times 2 and 4).ConclusionsAlthough both Ilizarov and Orthofix LRS fixation resolved the bone defects, external fixation had a negative impact on the patients’ mental health, which persisted even after removal of the devices. Although both methods led to negative effects on the patients’ mental, the impact of the Orthofix LRS was less severe.     

Prevalence of mood disorders according to dsm-iii-r criteria in the community elderly residents in Japan

The prevalence rates of mood disorders according to the DSM- III -R criteria in the community elderly were investigated with structured interviews conducted by psychiatrists. The subjects were 1,965 randomly selected residents aged 65 years or more who lived in Nagai City, Japan. In the first phase, a questionnaire including the short form of the Geriatric Depression Scale (GDS) was distributed to all subjects. In the second phase, all persons scoring 6 points or more on the GDS and approximately half as many of these persons randomly selected from the remaining respondents scoring 5 points or less were examined by psychiatrists using the A and D modules of the Structured Clinical Interview for DSM-III-R. The 1-month prevalence rates of major depression and bipolar disorder were estimated to be 0.9% and 0.0%, and the current prevalence of dysthymia was estimated to be 0.5%. By using additional unstructured clinical interviews, we also found the prevalence rates of adjustment disorder with depressed mood and other types of depression to be 3.8% and 2.5%. For these categories of depression, prevalence rates did not differ significantly by sex or age group, except that the prevalence of adjustment disorder with depressed mood was significantly higher in women than in men.     

Automated air kerma strength quality assurance of permanent seed implant prostate brachytherapy sources using vendor autoradiographs

PurposeTo develop a novel quality assurance (QA) program to determine the air kerma strength (AKS) of brachytherapy seeds within preloaded needles using autoradiographs alone, without jeopardizing sterility or necessitating procedural changes either by the vendor or in the operating room.Methods and MaterialsDigital autoradiographs of QA seed orders and sterile preloaded needles were acquired. Regions of interest of each preloaded seed were determined through an iterative scanning process identifying changes from background levels to radioactivity exposure. Average exposure values through the center of each region of interest were fitted with a Gaussian curve and Full Width at Half Maximums (FWHMs) were calculated. The two-dimensional exposure-scaled FWHM (Exp_2D) measurements for the QA seed orders were plotted against measured AKS values and related using a linear curve fit that was adjusted using the third-party assay average AKS and applied as a calibration curve to convert Exp_2D to AKS.ResultsEstimated seed AKS was found to have a strong dependence on position within the holding tray because of imager positioning inconsistencies. Calculated seed AKS for patient-specific seed orders using the curve scaling factor varied from the nominal order AKS by 1.1 ± 0.9% and from the third-party assay measurements by 0.0 ± 0.4%.ConclusionsThis work depicts a clinically useful tool to aid in QA of preloaded brachytherapy permanent seed implant needles without compromising sterility or increasing clinical workloads. With this procedure, each individual seed's AKS can be verified automatically before a patient's scheduled implant or retroactively when auditing patient records.     

以S2-R2为引物PCR检测石蜡切片中的孢子丝菌

目的 探讨应用特异性引物PCR方法检测石蜡切片中孢子丝菌的可行性。方法 选取30份大连及10份长春地区临床疑诊孢子丝菌病的石蜡切片标本,采用改良的微波脱蜡、液氮研磨-CTAB破壁法提取DNA,以特异性引物S2-R2进行PCR扩增,与真菌培养结果进行比对。结果 30份大连地区标本中22份见阳性PCR扩增产物（73.33%）。真菌培养阳性的22份标本中20份PCR出现阳性扩增产物（91%）,真菌培养阴性的8份标本中2 份PCR出现阳性扩增产物。10份长春地区标本7份见阳性PCR扩增产物（70%）。结论 以S2-R2为引物的 PCR适用于孢子丝菌病石蜡切片中病原菌的检测。     

脾宜健,肝宜疏,胃宜和——李振华教授治疗脾胃病思想

李振华教授认为:脾本虚证、无实证,脾宜健;治疗脾胃疾病,并非只从脾胃着眼,应注意从肝调治,肝宜疏;胃多实证,以通为用,以降为和,胃宜和.     

Psychological,Neuropsychological, and Electrocortical Effects of Mixed Mold Exposure

The authors assessed the psychological, neuropsychological, and electrocortical effects of human exposure to mixed colonies of toxigenic molds. Patients (N = 182) with confirmed mold-exposure history completed clinical interviews, a symptom checklist (SCL-90-R), limited neuropsychological testing, quantitative electroencephalogram (QEEG) with neurometric analysis, and measures of mold exposure. Patients reported high levels of physical, cognitive, and emotional symptoms. Ratings on the SCL-90-R were "moderate" to "severe," with a factor reflecting situational depression accounting for most of the variance. Most of the patients were found to suffer from acute stress, adjustment disorder, or post-traumatic stress. Differential diagnosis confirmed an etiology of a combination of external stressors, along with organic metabolically based dysregulation of emotions and decreased cognitive functioning as a result of toxic or metabolic encephalopathy. Measures of toxic mold exposure predicted QEEG measures and neuropsychological test performance. QEEG results included narrowed frequency bands and increased power in the alpha and theta bands in the frontal areas of the cortex. These findings indicated a hypoactivation of the frontal cortex, possibly due to brainstem involvement and insufficient excitatory input from the reticular activating system. Neuropsychological testing revealed impairments similar to mild traumatic brain injury. In comparison with premorbid estimates of intelligence, findings of impaired functioning on multiple cognitive tasks predominated. A dose-response relationship between measures of mold exposure and abnormal neuropsychological test results and QEEG measures suggested that toxic mold causes significant problems in exposed individuals. Study limitations included lack of a comparison group, patient selection bias, and incomplete data sets that did not allow for comparisons among variables.     

Low Doses of Allyphenyline and Cyclomethyline,Effective against Morphine Dependence,Elicit an Antidepressant-like Effect

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