Month of birth and risk of multiple sclerosis in a Portuguese population

Background

Several studies analyzing the month of birth (MOB) of multiple sclerosis (MS) patients and the risk of the disease have been published; as a whole, MS patients were found to be predominantly born in spring months, leading to the current assumption that MOB is somewhat related to the risk of MS.

Objective

Estimate the risk of MS by MOB in a Portuguese population.

Methods

MS patients sample was obtained from the database of patients attended at our MS clinic and born in the districts of Porto, Braga and Viana do Castelo. The control sample was composed of the live births records in the same time period and geographical area. We applied the Hewitt test for seasonality.

Results

We found 421 patients that satisfied the conditions to enter the study. The rank-sums for successive 6-month segments indicate the July–December period as of higher incidence; however, the corresponding rank-sum (48) was not statistically significant according to the Hewitt test (p > 0.05).

Conclusion

Our data does not support the seasonality hypothesis of MOB as risk factor for MS in Portugal. However we are aware that the analysis of a larger MS sample could shed more light in this issue.     

Contiguous ABCD1 DXS1357E deletion syndrome: Report of an autopsy case

Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is responsible for X‐linked adrenoleukodystrophy (X‐ALD), its phenotype differs from that of CADDS, which manifests with many features of Zellweger syndrome (ZS), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS, in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS. The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X‐ALD. Immunocytochemistry and Western blot showed the absence of ALD protein (ALDP) despite the presence of other peroxisomal proteins. Pathological studies disclosed a small brain with hypomyelination and secondary hypoxic‐ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal glioneuronal heterotopia indicated a neuronal migration disorder. The liver showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic. Array comparative genomic hybridization (CGH) analysis suggested that the deletion was a genomic rearrangement in the 90‐kb span starting in DXS1357E/BACP31 exon 4 and included ABCD1, PLXNB3, SRPK3, IDH3G and SSR4, ending in PDZD4 exon 8. Thus, the absence of ALDP, when combined with defects in the B‐cell antigen receptor associated protein 31 (BAP31) and other factors, severely affects VLCFA metabolism on peroxisomal functions and produces ZS‐like pathology.     

前列地尔对缺血性脑卒中的疗效及对脑源性神经营养因子和基质金属蛋白酶9的影响

目的 探讨前列地尔对缺血性脑卒中（Ischemic Stroke,IS）的临床疗效及其对脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）和基质金属蛋白酶9（matrix metalloproteinase 9,MMP-9）的影响.方法 将2007-06-2012-07在我院就诊的80例IS患者按照入院顺序随机分为前列地尔治疗组和对照组各40例.对照组采用常规治疗,前列地尔治疗组在常规治疗基础上每天加用20 μg前列地尔静滴治疗,持续14 d.比较2组临床疗效、BDNF和MMP-9的变化.结果 前列地尔组和对照组的总有效率分别为97.50%和80.00%;与治疗前相比,治疗后2组脑卒中量表（NIHSS ）评分均显著下降（P＜0.05）,而日常生活自理能力量表 （Activity of Daily Living Scale,ADL）评分则明显增高（P＜0.05）,经治疗2组BDNF含量均显著增加 （P＜0.05）,而MMP-9则明显下降（P＜0.05）,前列地尔组上述指标的改善程度均明显高于对照组 （P＜0.05）.结论 前列地尔能有效改善IS患者的临床症状,增加血浆BDNF水平及降低MMP-9含量可能是其治疗IS的可能作用机制.     

(E)-2-(2-Allylidenehydrazinyl)thiazole derivatives: Design,green synthesis,in silico and in vitro antimycobacterial and radical scavenging studies

By understanding the rampant infections of Mycobacterium tuberculosis (Mtb) and inflammations caused due to the generation of radical species during the Mtb infection, a series of (E)-2-(2-allylidenehydrazinyl)thiazole derivatives, with dual-action properties, was designed. The molecules were designed with a considerable variation in LogP, one of the critical parameters in physicochemical properties, and analyzed for their drug-likeness. For the synthesis, a simple, green, and multicomponent one-pot synthesis method was developed. The in vitro inhibition potentials were evaluated against Mtb H₃₇Rv by the microplate Alamar Blue assay. The results reveal that compound 6 was potent, with a MIC value of 6.5 µg/ml, and showed better interactions with the KasA protein with binding free energy (ΔG) of −9.4 kcal/mol. Also, the radical scavenging properties were studied to establish the dual-action properties of the molecules. Compound 9 exhibited promising antioxidant and nitric oxide radical scavenging activities, with 81.7% and 81.0%, respectively, at 1,000-μg/ml concentration.     

Radiographic predictors of IMRT for treating regional lymph nodes in breast cancer

Regional nodal irradiation (RNI) is an essential part of the treatment of high risk early stage (Stage IIb) and locally advanced (Stage III) breast cancer. Acceptable radiation plans can usually be achieved using 3-dimensional conformal radiation therapy with deep-inspiration breath hold to limit dose to the heart, although in some cases intensity-modulated radiation therapy produces superior results. The goal of this study is to identify radiographic parameters that predict the need for IMRT when delivering RNI. We retrospectively examined breast cancer patients treated with comprehensive RNI including internal mammary lymph nodes, supraclavicular lymph nodes, and undissected axillary lymph nodes at our institution from January 2016 to February 2018. Radiographic parameters including lung volume, internal mammary lymph nodes depth, modified central lung distance (mCLD), tangent length, and target height were recorded. Univariate and multivariate logistic regression was performed using IMRT as a binary endpoint (yes/no). A total of 46 patients were evaluated, of which 9 (20%) required IMRT. Five of the 9 (56%) IMRT patients were postmastectomy with a tissue expander in place. There was an increased likelihood of IMRT per 0.5 cm increase in mCLD (odds ratios [OR]: 3.27; 95% confidence interval [CI]: 1.39 to 9.63; p = 0.01) and per 1 cm increase in target height (OR: 1.77; 95% CI: 1.08 to 3.40; p = 0.04). A threshold value of 3.38 cm was identified for mCLD (OR 10.3; 95% CI: 2.14 to 61.4; p value = 0.005), and 25.2 cm for target height (OR 10.9; 95% CI: 2.19 to 82.7; p value = 0.007). When delivering RNI, larger values of mCLD and target height corresponded to the use of IMRT. Further investigations are warranted to confirm these findings, which may improve the efficiency of the treatment planning process and in turn patient care.     

Temporary Health Impact of Prostate MRI and Transrectal Prostate Biopsy in Active Surveillance Prostate Cancer Patients

PurposeTo assess the temporary health impact of prostate multiparametric MRI (mpMRI) and transrectal prostate biopsy in an active surveillance prostate cancer population.MethodsA two-arm institutional review board–approved HIPAA-compliant prospective observational patient-reported outcomes study was performed from November 2017 to July 2018. Inclusion criteria were men with Gleason 6 prostate cancer in active surveillance undergoing either prostate mpMRI or transrectal prostate biopsy. A survey instrument was constructed using validated metrics in consultation with the local patient- and family-centered care organization. Study subjects were recruited at the time of diagnostic testing and completed the instrument by phone 24 to 72 hours after testing. The primary outcome measure was summary testing-related quality of life (summary utility score), derived from the testing morbidities index (TMI) (scale: 0 = death and 1 = perfect health). TMI is stratified into seven domains, with each domain scored from 1 (no health impact) to 5 (extreme health impact). Testing-related quality-of-life measures in the two cohorts were compared with Mann-Whitney U test.ResultsIn all, 122 subjects were recruited, and 90% (110 of 122 [MRI 55 of 60, biopsy 55 of 62]) successfully completed the survey instrument. The temporary quality-of-life impact of transrectal biopsy was significantly greater than that of prostate mpMRI (0.82, 95% confidence interval [CI] 0.79-0.85, versus 0.95, 95% CI 0.94-0.97; P < .001). The largest mean domain-level difference was for intraprocedural pain (transrectal biopsy 2.6, 95% CI 2.4-2.8, versus mpMRI 1.3, 95% CI 1.1-1.5; P < .001).ConclusionTransrectal prostate biopsy has greater temporary health impact (lower testing-related quality-of-life measure) than prostate mpMRI.     

Training and Education Requirements for Authorized Users of Therapeutic Radiopharmaceuticals: Changes Under Consideration for 10CFR35.390 and Their Potential Impact

The US Nuclear Regulatory Commission (NRC) and 38 Agreement States have the regulatory authority to promulgate and enforce regulations related to the use of radioisotopes for medical purposes. Elements of these regulations include training and experience (T&E) requirements for individuals authorized to use the agents. These regulations are specified in 10CFR35.390. At this time, the NRC is considering significant revisions to the T&E requirements. This article describes current regulations and concerns related to the proposed changes and details the ACR organizational response.