Evaluation and evolution of apparent diffusion coefficient (ADC) in image-guided adaptive brachytherapy (IGABT) for cervical cancer

PURPOSEImage-guided adaptive brachytherapy (IGABT) recently has shown excellent clinical outcomes with superior local control and less toxicity. For IGABT, T2W (T2-weighted) MRI is the gold standard. However, studies have shown that target delineation with the same results in uncertainties, poor interobserver variabilities, and low conformity indices for high-risk clinical target volume contours. In this study, we investigate the role of diffusion-weighted imaging–derived apparent diffusion coefficient (ADC) maps to aid in IGABT. We also evaluated ADC from the baseline to brachytherapy.Methods and MaterialsThirty selected patients were enrolled for this study, and two MRIs were taken at diagnosis and before brachytherapy. Patients were divided into two groups, Group 1 being patients with parametrial involvement before external beam radiotherapy and no parametrial involvement before brachytherapy. Group 2 included patients with parametrial involvement before external beam radiotherapy and persistent parametrial involvement before brachytherapy. ADC was measured at the center, edge, and 1 cm from the edge.ResultsThe measured ADC increased from diagnosis to brachytherapy, and this increase was more for the patients in Group 1 than in Group 2. The mean TDadc (diagnosis ADC, center), TEadc (tumor edge ADC diagnosis), and T1cmDadc (1 cm from edge at diagnosis) were 0.884, 1.45, and 1.9 × 10^?3 mm²/s, respectively. The TBadc (ADC at brachytherapy, center), TEBadc (tumor edge ADC at brachytherapy), and TE1cmBadc (1 cm from edge brachytherapy) were 1.2, 1.8, and 2.3 × 10^?3 mm²/s, respectively, p-value <0.00001. No abnormal ADC was present outside the high-risk clinical target volume contours.ConclusionMRI-based IGABT using T2W imaging essentially covers all functionally abnormal zones at brachytherapy. Diffusion-weighted imaging, along with ADC maps, should only be used as a supplement for target delineation.     

Impacto de la Ley del tabaco en el lugar de trabajo: estudio de seguimiento de una cohorte de trabajadores en España 2005 – 07

Objective: The aim of this study is to describe the changes caused by the Law on Tobacco and its consumption in workers who are active smokers.DesignA post-intervention follow up study of a cohort of users.SettingHealth Centres in Valencia and Majorca.ParticipantsUsers who attended health centres.InterventionThe field work consisted of each patient filling in a case report form with the requested information.Main measurementsThe variables collected were, sex, place of work, education level, number of workers in the company, number of cigarettes smoked. They were told that on the following day they had to count the cigarettes smoked throughout the day, noting whether they had been smoked during or outside working hours. If they smoked during working hours, they reported whether it was inside or outside the workplace. On the following day they were telephoned to let us know the number of cigarettes smoked. This telephone call was repeated at six months and eighteen months.ResultsSmoking prevalence and the number of cigarettes smoked in the workplace has been reduced by 9% per month. The variables associated with compliance with the law were education level, the sex of the worker, and the size of the company.ConclusionsThe coming into force of the Tobacco Law has been effective.     

Connexin 43 in astrocytes contributes to motor neuron toxicity in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons in the CNS. Astrocytes play a critical role in disease progression of ALS. Astrocytes are interconnected through a family of gap junction proteins known as connexins (Cx). Cx43 is a major astrocyte connexin conducting crucial homeostatic functions in the CNS. Under pathological conditions, connexin expression and functions are altered. Here we report that an abnormal increase in Cx43 expression serves as one of the mechanisms for astrocyte‐mediated toxicity in ALS. We observed a progressive increase in Cx43 expression in the SOD1^G93A mouse model of ALS during the disease course. Notably, this increase in Cx43 was also detected in the motor cortex and spinal cord of ALS patients. Astrocytes isolated from SOD1^G93A mice as well as human induced pluripotent stem cell (iPSC)‐derived astrocytes showed an increase in Cx43 protein, which was found to be an endogenous phenomenon independent of neuronal co‐culture. Increased Cx43 expression led to important functional consequences when tested in SOD1^G93A astrocytes when compared to control astrocytes over‐expressing wild‐type SOD1 (SOD1^WT). We observed SOD1^G93A astrocytes exhibited enhanced gap junction coupling, increased hemichannel‐mediated activity, and elevated intracellular calcium levels. Finally, we tested the impact of increased expression of Cx43 on MN survival and observed that use of both a pan Cx43 blocker and Cx43 hemichannel blocker conferred neuroprotection to MNs cultured with SOD1^G93A astrocytes. These novel findings show a previously unrecognized role of Cx43 in ALS‐related motor neuron loss. GLIA 2016;64:1154–1169     

Serum calcium values in term and late-preterm neonates receiving gentamicin

Since noting an apparent increase in hypocalcemia in neonates receiving gentamicin every 24 h (q 24 h) for ≥ 4 days, we have prospectively monitored serum calcium (Ca) values in these patients receiving prolonged gentamicin therapy. This study is a retrospective analysis of those values measured during gentamicin treatment. The study included neonates with gestational age ≥ 35 weeks who received ≥ 4 days of gentamicin therapy and in whom at least one serum Ca value was measured ≥ 47 h after initiation of therapy. Hypocalcemia was defined as a serum Ca level < 8 mg/dl (2 mmol/l). Data were analyzed by Student t-test, chi-square test, and Pearson product moment correlation. There were 1,624 neonates that met the study criteria. Ca was < 8 mg/dl in 241 (15%). Ca < 8 mg/dl was more likely in boys than in girls (16.4% vs 11.8%, P = 0.01) and in neonates < 37 weeks gestational age (GA) than in those ≥ 37 weeks GA (23.9% vs 14.1%, P = 0.01). A second Ca value was obtained in 883 neonates (54%); 23.2% of neonates with initial Ca < 8 mg/dl remained hypocalcemic, and 30% of these were receiving oral Ca supplementation. The second Ca value was < 8 mg/dl in eight neonates in whom initial Ca was ≥ 8 mg/dl. Hypocalcemia is not uncommon in neonates receiving gentamicin therapy, and it may occur more frequently in boys and late-preterm infants. These data suggest that the monitoring of serum Ca levels should be considered when gentamicin is given ≥ 4 days. Presented in part at the Annual Meeting of the Pediatric Academic Societies, May 2006, San Francisco.     

High expression of p63 combined with a large N/C ratio defines a subset of human limbal epithelial cells: implications on epithelial stem cells

PURPOSE: To characterize human limbal epithelial cells based on the expression levels of nuclear protein p63 and the nucleus-to-cytoplasm (N/C) ratio. METHODS: Limbal, peripheral, and central corneal epithelia were separated from the stroma by Dispase II and subsequently were treated with trypsin to obtain single-cell suspensions. Cytospin smears of the cell suspensions were double immunostained for p63 and then stained for any one of the markers (acidic cytokeratins [AE1], K5, K3, or connexin 43 [Cx43]). They were counterstained with propidium iodide. More than 100 cells from each zone were analyzed for p63 expression levels and nuclear/cellular area using quantitative confocal microscopy. RESULTS: A gradient of p63-positive cells was observed in corneal and limbal epithelial cells. The percentage of p63-positive cells and the level of p63 expression were significantly higher in the limbal than in the peripheral or central corneal epithelium. Two-parameter (p63 levels and N/C ratio) analysis revealed the presence of a distinct population of small cells with higher levels of p63 and a large N/C ratio in the limbal epithelium. Such limbal epithelial cells were positive for AE1 and K5 but negative for K3 and Cx43. CONCLUSIONS: These results suggest that this distinct group of small cells in the limbal epithelium with greater N/C ratio, expressing high levels of nuclear protein p63, probably represent corneal epithelial stem cells.     

不同角膜仪测量的角膜曲率值的一致性分析

目的：比较测得后三种不同角膜仪测量的角膜曲率,以评估其测量值之间的一致性。

方法：前瞻性研究。252例患者(252眼)使用IOL Master(IM),Bausch & Lomb手动角膜仪(Man)以及TOPCON KR-8800自动角膜仪(Top)进行角膜曲率测量。记录并对比平均角膜曲率值。使用Bland Altman统计方法进行仪器间的一致性分析。

结果：1)IOL Master 和 手动角膜仪：IOL Master平均角膜曲率为44.62±1.52 D,手动角膜仪为44.60±1.52 D。 t-test显示差异具有统计学意义(P=0.001); Bland-Altman图显示两种仪器间95%一致性区间(LOAs)为-0.22～0.22; 2)IOL Master 和自动角膜仪：IOL Master平均角膜曲率为44.62±1.52 D,自动角膜仪为44.46±1.53 D。t-test显示差异具有统计学意义(P<0.0001)。Bland-Altman图显示两种仪器间95%LOAs为 -0.24～0.55; 3)自动角膜仪和手动角膜仪：自动角膜仪平均角膜曲率为44.60±1.52 D,手动角膜仪为44.46±1.53 D。t-test显示差异具有统计学意义(P<0.0001)。Bland-Altman图显示两种仪器间95%LOAs为-0.30～0.57。

结论：使用不同的仪器获得的角膜曲率数据是不可替换的,这对于白内障外科医生在外科手术计划和结果评估方面具有重要意义。