Sleep-wake rhythm in an irregular shift system

Sleep in shift work has been studied extensively in regular shift systems but to a lesser degree in irregular shifts. Our main aim was to examine the sleep-wake rhythm in shift combinations ending with the night or the morning shift in two irregular shift systems. Three weeks' sleep/work shift diary data, collected from 126 randomly selected train drivers and 104 traffic controllers, were used in statistical analyses including a linear mixed model and a generalized linear model for repeated measurements. The results showed that the sleep-wake rhythm was significantly affected by the shift combinations. The main sleep period before the first night shift shortened by about 2 h when the morning shift immediately preceded the night shift as compared with the combination containing at least 36 h of free time before the night shift (reference combination). The main sleep period before the night shift was most curtailed between two night shifts, on average by 2.9 and 3.5 h among the drivers and the controllers, respectively, as compared with the reference combination. Afternoon napping increased when the morning or the day shift immediately preceded the night shift, the odds being 4.35-4.84 in comparison with the reference combination. The main sleep period before the morning shift became 0.5 h shorter when the evening shift preceded the morning shift in comparison with the sleep period after a free day. The risk for dozing off during the shift was associated only with the shift length, increasing by 17 and 35% for each working hour in the morning and the night shift, respectively. The results demonstrate advantageous and disadvantageous shift combinations in relation to sleep and make it possible to improve the ergonomy of irregular shift systems.     

Expression of human pim family genes is selectively up-regulated by cytokines promoting T helper type 1, but not T helper type 2, cell differentiation

Cytokines are the most important inducers of T helper (Th) cell differentiation. Interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) are responsible for human Th1-cell differentiation, while IL-4 is the critical cytokine promoting Th2-cell development. These two subsets of cells co-ordinate immunological responses to pathogens as well as autoimmune or allergic reactions. The pim family of proto-oncogenes encodes serine/threonine-specific kinases involved in cytokine-mediated signalling pathways in haematopoietic cells. Here we demonstrate that expression of pim-1 and pim-2 mRNAs is selectively up- or down-regulated in human cord-blood-derived CD4+ cells freshly induced to polarize towards Th1 or Th2 cells, respectively, whereas their expression is inhibited in both cell types by the immunosuppressive transforming growth factor beta (TGF-beta). Moreover, the Th1-specific cytokines IL-12 and IFN-alpha, but not the Th2-specific cytokine IL-4, transiently up-regulate pim-1 and pim-2 mRNA expression in human peripheral blood T cells and natural killer cells. In addition, the Pim-1 protein levels are strongly up-regulated by Th1-specific cytokines in all of these cell types. Taken together, our results suggest that pim genes and their protein products are involved in the early differentiation process of T helper cells.     

A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy

Mulibrey nanism is a rare autosomal-recessive disorder characterized by prenatal onset severe growth retardation and pericardial constriction associated with abnormalities of muscle, liver, brain and eye. More than 80% of previously reported patients are of Finnish origin in whom a founder mutation in the TRIM37 gene have been described. We report on a 7-year-old Turkish boy who presented with classical phenotypic features of mulibrey nanism. Mutation screening of the TRIM37 gene revealed that the proband had a homozygous two base pair deletion, c.1894_1895delGA, resulting in a frame-shift and a premature termination codon. Our proband is one of the rare examples of mulibrey nanism outside Finland and extends the mutation spectrum in this disorder.     

SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma – a Nordic Lymphoma Group study

Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment‐related morbidity, additional parameters need to be evaluated to enable risk‐adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki‐67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.     

White adipose tissue mitochondrial metabolism in health and in obesity

White adipose tissue is one of the largest organs of the body. It plays a key role in whole‐body energy status and metabolism; it not only stores excess energy but also secretes various hormones and metabolites to regulate body energy balance. Healthy adipose tissue capable of expanding is needed for metabolic well‐being and to prevent accumulation of triglycerides to other organs. Mitochondria govern several important functions in the adipose tissue. We review the derangements of mitochondrial function in white adipose tissue in the obese state. Downregulation of mitochondrial function or biogenesis in the white adipose tissue is a central driver for obesity‐associated metabolic diseases. Mitochondrial functions compromised in obesity include oxidative functions and renewal and enlargement of the adipose tissue through recruitment and differentiation of adipocyte progenitor cells. These changes adversely affect whole‐body metabolic health. Dysfunction of the white adipose tissue mitochondria in obesity has long‐term consequences for the metabolism of adipose tissue and the whole body. Understanding the pathways behind mitochondrial dysfunction may help reveal targets for pharmacological or nutritional interventions that enhance mitochondrial biogenesis or function in adipose tissue.     

Automated GMP production and long-term experience in radiosynthesis of CB1 tracer [18F]FMPEP-d2

Here, we describe the development of an in-house-built device for the fully automated multistep synthesis of the cannabinoid CB₁ receptor imaging tracer (3R,5R)-5-(3-([¹⁸F]fluoromethoxy-d₂)phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([¹⁸F]FMPEP-d₂), following good manufacturing practices. The device is interfaced to a HPLC and a sterile filtration unit in a clean room hot cell. The synthesis involves the nucleophilic ¹⁸F-fluorination of an alkylating agent and its GC purification, the subsequent ¹⁸F-fluoroalkylation of a precursor molecule, the semipreparative HPLC purification of the ¹⁸F-fluoroalkylated product, and its formulation for injection. We have optimized the duration and temperature of the ¹⁸F-fluoroalkylation reaction and addressed the radiochemical stability of the formulated product. During the past 5 years (2013–2018), we have performed a total of 149 syntheses for clinical use with a 90% success rate. The activity yield of the formulated product has been 1.0 ± 0.4 GBq starting from 11 ± 2 GBq and the molar activity 600 ± 300 GBq/μmol at the end of synthesis.     

Surgery for stress urinary incontinence in Finland 1987–2009

Introduction and hypothesis

To estimate the incidence rates of stress urinary incontinence (SUI) surgery among Finnish women from 1987 to 2009 by age, and to evaluate the trends in SUI surgery.

Methods

We conducted a retrospective register-based study. All SUI procedures on adult women over age 18 years in Finland were identified from the nationwide Care Register for Health Care. Age-specific incidence rates per 1,000 women were calculated for each year. The cumulative incidence of SUI surgery was calculated.

Results

There were 38,340 procedures for SUI in 1987–2009. The overall age-adjusted incidence rate increased 2.6-fold from 0.5/1,000 women in 1987 to 1.3/1,000 in 2002, but declined thereafter by 2009 to 0.8/1,000. There was a six-fold increase in the incidence rate in the age group 60–69 years and a ten-fold increase in the age group 70–79 years from 1987 to 2002. These marked increases in operation rates coincided with the increased use of tension-free vaginal tape (TVT). In 2002, TVT accounted for 96 % of all SUI procedures. Mid-urethral slings with transobturator techniques surpassed TVT in popularity in 2007. The life-long cumulative incidence of SUI surgery was 9.9 % in 2002 and 6.3 % in 2009.

Conclusions

The incidence rates of SUI surgery increased significantly in Finland, especially among women aged 60 to 79 years. Mid-urethral slings have become the dominant procedure.