Immunoexpression of Androgen Receptor in the Nontumorous Pituitary and in Adenomas

Little information is available regarding androgen receptor immunoexpression (AR) in the normal and neoplastic human pituitary. Available experimental data links it to primarily gonadotroph cells. We undertook an immunohistochemical study of 41 autopsy-derived normal glands from patients of both sexes and all ages as well as 79 fully characterized pituitary adenomas of all types, the focus being upon AR expression in normal and neoplastic gonadotrophs. Nuclear AR immunoreactivity was noted in gonadotrophs and other normal adeno- and neurohypophysial cells. In addition to its presence in 74% of gonadotroph and 55% of null cell adenomas, lesser proportions of other adenoma types (adrenocorticotropic hormone 50%, prolactin 38%, growth hormone 33%) also exhibited AR immunoreactivity. No staining of thyroid-stimulating hormone adenomas was noted. The physiologic significance of our findings remains to be explored. The literature regarding AR expression in animal and human pituitaries is reviewed.     

前房注射0.1%莫西沙星联合结膜下注射曲安奈德预防超声乳化术后感染

目的：评估前房注射0.1% 莫西沙星联合结膜下注射4 mg曲安奈德预防白内障超声乳化术后感染和炎症的疗效,并与局部滴药组比较。

方法：共纳入1000例,平均年龄38～70岁,全部行超声乳化术的患者分为两组,两组在年龄、术前眼压(IOP)和中心黄斑厚度(CMT)方面无显著差异,分别为P=0.6, P=0.9 和P=0.8。对照组患者500例,术后1mo每日4次局部应用0.5%盐酸莫西沙星和0.1%地塞米松滴眼液。研究组在手术结束时,前房注入0.1%莫西沙星0.4 mL联合4 mg曲安奈德结膜下注射。随访时间为术后1d、1wk、1mo和3mo。检查4次前房反应,测量3次眼压,最后一次测量CMT。

结果：该临床试验研究中两组人群分别应用不同的预防方法,两组无眼内炎病例发生。通过两样本t检验,术后1d,研究组前房细胞显著低于对照组,而术后1wk、1mo和3mo两组间无统计学差异。在第3mo随访时,两组间眼压和中心黄斑厚度无明显差异。对照组炎症发生率为9.6%,研究组为4%。对照组在1mo时眼压升高≥10 mmHg患者占2.4%, 显著高于研究(0.8%)。

结论：白内障术后联合应用前房内莫西沙星和结膜下曲安奈德可有效预防感染和炎症,并且大多数(480例)患者不需其它任何外用药物, 这为患者节省了成本, 并帮助降低无法实施局部用药的病人并发症的几率与依从性差的患者术后不良药物反应。     

The efficacy and safety of bimatoprost/timolol maleate,latanoprost/timolol maleate,and travoprost/timolol maleate fixed combinations on 24-h IOP

Purpose

To evaluate the effect of bimatoprost/timolol maleate fixed combination (BTFC), latanoprost/timolol maleate fixed combination (LTFC), and travoprost/timolol maleate fixed combination (TTFC) on 24-h intraocular pressure (IOP) in patients with open-angle glaucoma.

Methods

This prospective, observer-masked, randomized study included 50 patients with primary open-angle glaucoma. All patients were using hypotensive lipids and timolol maleate fixed combination treatment for ≥4 weeks and had an IOP ≤ 21 mmHg. Group 1 (n = 18) received BTFC, group 2 (n = 14) received LTFC, and group 3 (n = 18) received TTFC. All patients were hospitalized, and IOP was monitored for 24-h (10:00, 14:00, 18:00, 22:00, 02:00, and 06:00). Mean diurnal IOP variation measurements were taken between 06:00 and 18:00, and mean nocturnal IOP variation measurements were taken between 22:00 and 02:00. Mean IOP and IOP variation in the three groups were compared.

Results

Mean 24-h IOP did not differ significantly between the three groups (group 1: 14.6 ± 2.9 mmHg; group 2: 14.1 ± 3.7 mmHg and group 3: 15.8 ± 2.0 mmHg; P > 0.05). Mean diurnal IOP variation was 4.6 ± 2.3 mmHg in group 1, 5.8 ± 2.4 mmHg in group 2, and 4.3 ± 1.7 mmHg in group 3, and mean nocturnal IOP variation was 3.2 ± 2.8 mmHg in group 1, 2.9 ± 1.9 mmHg in group 2, and 3.0 ± 1.6 mmHg group 3. There were not any significant differences in diurnal or nocturnal IOP variation between the three groups (P < 0.05).

Conclusion

All three fixed combinations effectively controlled IOP for 24-h and had a similar effect on diurnal and nocturnal IOP variations.

     

The influence of chronic diseases and poor working conditions in working life expectancy across educational levels among older employees in The Netherlands

ObjectivesThis study aims to estimate the influence of chronic diseases and poor working conditions – across educational levels – on working life expectancy (WLE) and working years lost (WYL) in the Dutch workforce after age 50.MethodsInformation on demographics, chronic diseases, and working conditions from 11 800 Dutch workers aged 50–66 years participating in the Study on Transitions in Employment, Ability and Motivation (STREAM) from 2010/2015 was enriched with monthly information on employment status from Statistics Netherlands up to 2018. In a multistate model, transitions were calculated between paid employment and involuntary exit (disability benefits, unemployment) and voluntary exit (economic inactivity, early retirement) to estimate the impact of education, chronic diseases, and working conditions on WLE and WYL between age 50 and 66.ResultsWorkers with a chronic disease (up to 1.01 years) or unfavorable working conditions (up to 0.63 years) had more WYL due to involuntary pathways than workers with no chronic disease or favorable working conditions. The differences in WYL between workers with and without a chronic disease were slightly higher among workers with a lower education level (male: 0.85, female: 1.01 years) compared to workers with a high educational level (male: 0.72, female: 0.82 years). Given the higher prevalence of chronic diseases and unfavorable working conditions, WYL among lower educated workers were higher than among higher educated workers.ConclusionsThe presence of a chronic disease or unfavorable working conditions, more prevalent among lower educated workers, contribute substantially to WYL among older workers. This will increase educational inequalities in working careers.     

The effect of erythroferrone suppression by transfusion on the erythropoietin–erythroferrone–hepcidin axis in transfusion-dependent thalassaemia: A pre–post cohort study

To track post-transfusion changes on the erythropoietin (EPO)–erythroferrone (ERFE)–hepcidin axis, we collected blood samples from 82 regularly transfused patients with β-thalassaemia major (β-TM) immediately before and 4–6 days after transfusion. The post-transfusion haemoglobin, hepcidin, and ferritin levels were increased, while the EPO, ERFE, and soluble transferrin receptor were suppressed. In addition, hepcidin change was inversely associated with erythropoietic change, which was confirmed by an increase in the hepcidin-to-ERFE ratio after transfusion. Age was the main predictor of serum ERFE, followed by EPO, transfusion frequencies, and ferritin. We found ERFE to be a highly sensitive indicator of erythroid activity in β-TM and that the hepcidin-to-ERFE ratio after transfusion may be used as an appropriateness index of serum hepcidin regulation relative to the degree of erythropoiesis.     

Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child–parent trios and a case–control design to identify novel rare variants

The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child–parent trios, one child–mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case–control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex.     

NDE1-related disorders: A recurrent NDE1 pathogenic variant causing Lissencephaly 4 can also be associated with microhydranencephaly

NudE Neurodevelopment Protein 1 (NDE1) gene encodes a protein required for microtubule organization, mitosis, and neuronal migration. Biallelic pathogenic variants of NDE1 gene are associated with structural central nervous system abnormalities, specifically microlissencephaly and microhydranencephaly. The root of these different phenotypes remains unclear. Here, we report a 20-year-old male patient referred to our clinics due to severe microcephaly, developmental delay, spastic quadriplegia, and dysmorphic features. The cranial computed tomography revealed abnormal brain structure and excess of cerebrospinal fluid, consistent with microhydranencephaly. A homozygous c.684_685del, p.(Pro229TrpfsTer85) change in NDE1 gene was found by clinical exome analysis. The variant has previously been reported in individuals with microlissencephaly, therefore we propose that the same variant within the gene may cause either microlissencephaly or microhydranencephaly phenotypes. There are only a few papers about NDE1-related disorders in the literature and the patient we described is important to clarify the phenotypic spectrum of the disease.