Functional connectivity reveals load dependent neural systems underlying encoding and maintenance in verbal working memory

One of the main challenges in working memory research has been to understand the degree of separation and overlap between the neural systems involved in encoding and maintenance. In the current study we used a variable load version of the Sternberg item recognition test (two, four, six, or eight letters) and a functional connectivity method based on constrained principal component analysis to extract load-dependent neural systems underlying encoding and maintenance, and to characterize their anatomical overlap and functional interaction. Based on the pattern of functional connectivity, constrained principal component analysis identified a load-dependent encoding system comprising bilateral occipital (Brodmann's area (BA) 17, 18), bilateral superior parietal (BA 7), bilateral dorsolateral prefrontal (BA 46), and dorsal anterior cingulate (BA 24, 32) regions. For maintenance, in contrast, constrained principal component analysis identified a system that was characterized by both load-dependent increases and decreases in activation. The structures in this system jointly activated by maintenance load involved left posterior parietal (BA 40), left inferior prefrontal (BA 44), left premotor and supplementary motor areas (BA 6), and dorsal cingulate regions (BA 24, 32), while the regions displaying maintenance-load-dependent activity decreases involved bilateral occipital (BA 17, 18), posterior cingulate (BA 23) and rostral anterior cingulate/orbitofrontal (BA 10, 11, 32) regions. The correlation between the encoding and maintenance systems was strong and negative (Pearson's r = -.55), indicting that some regions important for visual processing during encoding displayed reduced activity during maintenance, while subvocal rehearsal and phonological storage regions important for maintenance showed a reduction in activity during encoding. In summary, our analyses suggest that separable and complementary subsystems underlie encoding and maintenance in verbal working memory, and they demonstrate how constrained principal component analysis can be employed to characterize neuronal systems and their functional contributions to higher-level cognition.     

Methotrexate, bleomycin, and Etoposide in the treatment of gestational trophoblastic neoplasia

OBJECTIVE: The combination of methotrexate (1 g/m(2) day 1), bleomycin (10 mg day 3), and etoposide (100 mg/m(2) days 1-5) (MBE) has been used for disease relapse or as a second-line chemotherapy in the treatment of gestational trophoblastic neoplasia (GTN) resistant to multiple-agent chemotherapy. With the identification of ultra-high-risk GTN, MBE has also been used as first-line chemotherapy. The current study is to review the use of MBE in the treatment of GTN. METHODS: Patients who received MBE for GTN between 1985 and 2003 in Queen Mary Hospital were included in this study. Records were reviewed and data were analyzed. Outcomes including response rate, treatment complications, and survival were assessed. RESULTS: Methotrexate, bleomycin, and etoposide therapy was given as first line to 4 patients with ultra-high-risk GTN. Three responded to the treatment and remained disease free. Methotrexate, bleomycin, and etoposide were given as a second-line therapy to 8 patients who had drug resistance to the initial therapy. Seven responded, and 6 remained disease free at 5 years. Methotrexate, bleomycin, and etoposide were given as a second-line therapy to 8 patients who relapsed 2-18 months after their initial therapy. Seven patients responded, and 4 remained disease-free at 5 years, 2 defaulted, and one died of carcinoma of the colon. Of the 20 patients who received MBE, 12 developed grade 3/4 neutropenia, and 4 developed grade 3/4 thrombocytopenia. The overall response rate for MBE was 85%. CONCLUSION: Methotrexate, bleomycin, and etoposide should be considered as a second-line therapy in patients who have drug-resistant or recurrent GTN.     

煅烧骨的安全性

背景：经高温处理的煅烧骨具有类似自然骨的连续微孔结构,良好的生物相容性和降解性。 目的：观察牛煅烧骨的生物相容性、细胞相容性及毒性。 方法：①细胞相容性实验：将牛煅烧骨与第3 代已诱导的Wistar大鼠骨髓间充质干细胞复合培养。②溶血实验：将煅烧骨浸提液、生理盐水与双蒸水加入兔血中。③凝血实验：将煅烧骨加入兔血浆中。④急性毒性实验：在昆明种小鼠尾静脉分别注射煅烧骨浸提液、生理盐水。⑤微核实验：在小鼠腹腔分别注射煅烧骨浸提液、生理盐水与环磷酰胺。⑥局部刺激性实验：将煅烧骨浸提液、生理盐水分别注射于兔两侧脊柱皮下。⑦热源检测实验：在兔耳静脉注射煅烧骨浸提液。⑧皮下植入实验：将煅烧骨材料植入Wistar大鼠背部皮下。 结果与结论：煅烧骨材料无细胞毒性,具有良好的细胞及血液相容性;对皮肤、肌肉无刺激作用;对心、肝、肾重要器官无毒性作用;皮下植入后对周围组织无刺激作用,能够部分降解吸收并被机体组织替代;无致热作用,对凝血功能无影响,对小鼠骨髓细胞无抑制及毒性作用。     

Risk factors for fracture in adult kidney transplant recipients

AIM: To determine the general and transplant-specific risk factors for fractures in kidney transplant recipients. METHODS: We conducted a cohort study of all adults who received a kidney-only transplant (n = 2723) in Ontario, Canada between 2002 and 2009. We used multivariable Cox proportional hazards regression to determine general and transplant-specific risk factors for major fractures (proximal humerus, forearm, hip, and clinical vertebral). The final model was established using the backward elimination strategy, selecting risk factors with a P-value ≤ 0.2 and forcing recipient age and sex into the model. We also assessed risk factors for other fracture locations (excluding major fractures, and fractures involving the skull, hands or feet). RESULTS: There were 132 major fractures in the follow-up (8.1 fractures per 1000 person-years). General risk factors associated with a greater risk of major fracture were older recipient age [adjusted hazard ratio (aHR) per 5-year increase 1.11, 95%CI: 1.03-1.19] and female sex (aHR = 1.81, 95%CI: 1.28-2.57). Transplant-specific risk factors associated with a greater risk of fracture included older donor age (5-year increase) (aHR = 1.09, 95%CI: 1.02-1.17) and end-stage renal disease (ESRD) caused by diabetes (aHR = 1.72, 95%CI: 1.09-2.72) or cystic kidney disease (aHR = 1.73, 95%CI: 1.08-2.78) (compared to glomerulonephritis as the reference cause). Risk factors across the two fracture locations were not consistent (major fracture locations vs other). Specifically, general risk factors associated with an increased risk of other fractures were diabetes and a fall with hospitalization prior to transplantation, while length of time on dialysis, and renal vascular disease and other causes of ESRD were the transplant-specific risk factors associated with a greater risk of other fractures. CONCLUSION: Both general and transplant-specific risk factors were associated with a higher risk of fractures in kidney transplant recipients. Results can be used for clinical prognostication.     

Knowledge,attitudes, and communication around human papillomavirus (HPV) vaccination amongst urban Asian mothers and physicians

To determine why HPV vaccination uptake is low in Asia, we surveyed attitudes, knowledge and communication about cervical cancer and HPV vaccination amongst 480 physicians and 1617 randomly selected urban mothers who could afford HPV vaccines in Korea, Malaysia, Taiwan and Thailand. HPV vaccine rejection by mothers was linked with poor knowledge and low perceptions of self-relevance. Physicians’ likelihood of raising the subject and/or recommending vaccination was linked to how proactively they advocate preventive health, their attitude to the subject's sensitivity and their knowledge levels. Because most Asian mothers seek doctors’ advice and prefer them to take the initiative, physicians should be more proactive in discussing and recommending HPV vaccination.     

Proto-oncogenes and p53 protein expression in normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia

The aim of this study was to study the protein expression of six proto-oncogenes (epidermal growth factor receptor (EGFR), c-fms, c-myc, c-kit, c-erbB-2 and pan-ras) and one tumour suppressor gene (TP53), by immunohistochemical staining of normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia (CIN). Paraffin sections of 45 normal cervical specimens, 38 CIN grade one (CIN1), 37 CIN2 and 43 CIN3 were studied. An immunohistochemical (IHC) score was derived from the intensity of staining and the percentages of cells stained. In normal cervical specimens, a higher IHC score was found with EGFR and c-fms in superficial (S), intermediate (I) and parabasal (PB) cells compared with basal cells. In contrast, a higher IHC score was found with c-erbB-2 in basal cells in normal cervical specimens. Dysplastic cells in CIN had a higher IHC score with c-myc and c-erbB-2 than normal S/I and PB cells. Dysplastic cells had a higher score with EGFR than normal basal cells. However, a higher IHC score with EGFR and c-fms was found in normal S/I cells than dysplastic cells. These findings suggested that EGFR and c-fms were activated in more differentiated normal cells but were less active in less differentiated normal basal cells. However, EGFR was reactivated in dysplastic cells. Meanwhile, c-erbB-2 was activated in less differentiated normal basal cells and dysplastic cells, and was less active in differentiated normal cells. c-myc was activated in dysplastic cells. c-fms was more active in more differentiated normal cells and was not activated in less differentiated or dysplastic cells. c-kit, pan-ras and TP53 were not activated in normal nor dysplastic cervical cells. These results suggest EGFR, c-erbB-2 and c-myc may be important proto-oncogenes in CIN and that antibodies or anti-genes targeted against them may alter the progress of CIN to invasive cancer.     

Approach to diagnosis and treatment of pediatric primary tumors of the diaphragm

Background/Purpose

Tumors of the diaphragm in the pediatric population are extremely rare. We present 5 cases diagnosed at the Hospital for Sick Children, Toronto, and together with a review of the world literature, provide an approach to the diagnosis and management of these tumors.

Methods

A clinical retrospective review of patients diagnosed as having primary diaphragmatic tumor (PDT) at the Hospital for Sick Children as well as a review of the world literature.

Results

Forty-one cases of PDT in the pediatric population have been described from 1868 to 2005 inclusive. There is an equal incidence in boys and girls, they are found with the same frequency on the left as on the right, and 78% are malignant. Rhabdomyosarcoma is the most commonly occurring malignant tumor. The mean age at diagnosis is 10 years. “Chest-associated” symptoms are more common than “abdomen-associated” symptoms. Imaging often fails to identify the site of origin as the diaphragm. Surgery is the cornerstone of therapy for PDT.

Conclusion

A multidisciplinary team approach is needed for successful treatment and management of PDT.     

A randomised double-blinded controlled trial of the effect of diluent volume on the efficacy of a single dose of epidural ropivacaine for labour analgesia

BACKGROUND: Few studies have systematically investigated the effect of diluent volume on the efficacy of epidural local anaesthetics for labour analgesia and no data are available for ropivacaine. Our aim was to compare epidural ropivacaine given in three different volumes for labour analgesia. METHODS: In a double-blinded study, we randomly assigned 60 labouring parturients with cervical dilatation <5 cm to receive epidural ropivacaine 30 mg diluted to 5 mL (group 5, n=20), 10 mL (group 10, n=20) or 20 mL (group 20, n=20) for analgesia. We measured visual analogue scale pain scores at the peak of contraction for 30 min plus onset and duration of analgesia. RESULTS: Pain scores at 30 min were similar among group 5 (median 22 [interquartile range 0-44] mm), group 10 (9 [0-21] mm) and group 20 (37 [0-51] mm), P=0.35. The number of patients who achieved a decrease in pain score to < or =30% of baseline was similar among group 5 (12/20 (60%)), group 10 (17/20 (85%)) and group 20 (11/19 (58%)), P=0.13. Onset and duration of analgesia, the incidence of motor block and patient satisfaction were similar among groups. CONCLUSIONS: Under the conditions of this study, within the range of 5-20 mL, the volume and concentration were not significant factors influencing the efficacy of a single 30-mg bolus of epidural ropivacaine given for labour analgesia. This suggests that the most important factor influencing analgesic efficacy was drug mass.