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BackgroundCentral hypothyroidism (CeH) is a rare condition affecting approximately 1:16 000- 100 000 individuals. Congenital forms can harm normal development if not detected and treated promptly. Clinical and biochemical diagnosis, especially of isolated CeH, can be challenging. Cases are not usually detected in neonatal screening, which, in most countries, is focused on detection of the more prevalent primary hypothyroidism. Until now, five genetic causes for isolated CeH have been identified. Here we aimed to identify the genetic cause in two brothers with impaired growth diagnosed with CeH at the age of 5 years. We further evaluated the candidate gene variants in a large genetic database.MethodsClinical and biochemical characterization together with targeted next-generation sequencing (NGS) was used to identify the genetic cause in a family of two brothers presenting with CeH. Screening of insulin receptor substrate 4 (IRS4) variants was carried out in the FinnGen database.ResultsA novel monoallelic frameshift mutation c.1712_1713insT, p.Gly572Trp fs*32 in the X-linked IRS4 gene was identified by NGS analysis in both affected males and confirmed using Sanger sequencing. Their mother was an unaffected carrier. In addition to the declined growth at presentation, central hypothyroidism and blunted TRH test, no other phenotypic alterations were found. Diagnostic tests included head MRI, thyroid imaging, bone age, and laboratory tests for thyroid autoantibodies, glucose, insulin and glycosylated hemoglobin levels. Examination of the IRS4 locus in FinnGen (R5) database revealed the strongest associations to a rare Finnish haplotype associated with thyroid disorders (p = 1.3e-7) and hypothyroidism (p = 8.3e-7).ConclusionsHere, we identified a novel frameshift mutation in an X-linked IRS4 gene in two brothers with isolated CeH. Furthermore, we demonstrate an association of IRS4 gene locus to a general thyroid disease risk in the FinnGen database. Our findings confirm the role of IRS4 in isolated central hypothyroidism.

Pregnancy – induced hypertension (PIH), preeclampsia (PE), and gestational diabetes (GDM) are common adverse outcomes in pregnancy. To find out whether preconceptual leptin levels differ in subsequent pregnancy between control vs. GDM and hypertensive pregnancy groups. Data was from The Cardiovascular Risk in Young Finns Study and The Medical Birth Register of Finland. Of 293 subjects 71 developed GDM, 27 PIH/PE and 201 were controls. Leptin was higher in GDM (p < 0.0001) and PIH/PE (p = 0.0002) groups compared to control. GDM group was robust to BMI matching (p = 0,0081). Leptin was higher in GDM (p < 0.0001) and PIH/PE (p = 0.0002) groups compared to control. GDM group was robust to BMI matching (p = 0,0081). [ABSTRACT FROM AUTHOR]

Modified wood fibres open new perspectives to create value-added products based on renewable raw materials. An interesting option is the targeted modification of fibre surfaces by oxidative enzymes. This two-stage functionalisation method consists of enzymatic activation of fibre surfaces followed by addition of radicalised compounds reacting preferentially by radical coupling. In this work, the activation of bleached and unbleached softwood TMPs with laccase isolated from Trametes hirsuta was studied. The formation and stability of the radicals were studied by EPR spectroscopy. The reaction of the radicals with 3-hydroxytyramine hydrochloride and the type of chemical linkages were investigated. EPR, ESCA and FTIR spectroscopy were used for analysis. Bleached TMP was radicalised more efficiently than unbleached TMP. The radicals were unstable, as 90% of them were quenched within a few hours. Their lifetime was, however, found to be adequately long for performing coupling reactions. Bonding of new compounds to pulps via radical reactions thus seems to be possible. [ABSTRACT FROM AUTHOR]

Background. We tested the hypothesis that depressive symptoms in healthy young adults would be associated with elevated levels of C-reactive proteins (CRP).Method. We studied the association between depressive symptoms and CRP in 1201 young adults, as a part of the on-going population-based Cardiovascular Risk in Young Finns Study. Depressive symptoms were determined by responses to a revised version of Beck's Depression Inventory in 1992 and 2001. CRP and other known cardiac risk factors were measured in 2001.Results. Higher depressive symptomatology in 1992 and in 2001 and their means score were related to higher CRP levels (B's range from 0·24 to 0·21, p<0·001). These relationships persisted after separate adjustments for various risk factors including sex, age, education, oral contraceptive use, dietary fat, physical activity, alcohol consumption, smoking status, LDL-cholesterol, HDL-cholesterol, systolic blood pressure and history of acute infectious disease. Adjustments for obesity and triglycerides levels, however, somewhat attenuated the relationship between depressive symptoms and CRP.Conclusions. We concluded that higher levels of depressive symptoms are associated with higher levels of CRP, but this association may largely be attributable to obesity or triglycerides. [ABSTRACT FROM AUTHOR]

The actinobacterium Streptomyces cyaneus CECT 3335 was evaluated for its ability to delignify spruce wood chips (Picea abies) after 2 weeks of incubation prior to refiner mechanical pulping. Weight loss of the chips during the treatment ranged from 2% to 3%. Chemicalanalysis of the treated wood showed an increase in acid-soluble lignin content concomitant with a notable increase in the acid/aldehyde+ketone [AC/(AL+KE)] ratio of the lignin compared with the control. Structural alterations in wood cell walls were observed by optical and scanning microscopy using astra blue-safranin staining and cryosections stained with gold/palladium, respectively. A gradual loss of lignin from the lumen towards the middle lamella and incipient defiberization could be observed. The estimation of specific energy for the defibration and refining stages of treated pulp showed a 24% reduction in the energy required, largely due to a 30% saving in the defibration of chips. The analysis of handsheets obtained from treated pulp showed a notable improvement in some strength properties, such as breaking length, tear index and stretch. In addition, the high Gurley air resistance value indicates more packing of the voids of the fiber network. These results demonstrate for the first time the suitability of Streptomyces cyaneus for biomechanical pulping purposes. [ABSTRACT FROM AUTHOR]

The wet oxidation pretreatment (water, oxygen, elevated temperature, and pressure) of softwood (Picea abies) was investigated for enhancing enzymatic hydrolysis. The pretreatment was preliminarily optimized. Six different combinations of reaction time, temperature, and pH were applied, and the compositions of solid and liquid fractions were analyzed. The solid fraction after wet oxidation contained 58-64% cellulose, 2-16% hemicellulose, and 24-30% lignin. The pretreatment series gave information about the roles of lignin and hemicellulose in the enzymatic hydrolysis. The temperature of the pretreatment, the residual hemicellulose content of the substrate, and the type of the commercial cellulase preparation used were the most important factors affecting the enzymatic hydrolysis. The highest sugar yield in a 72-h hydrolysis, 79% of theoretical, was obtained using a pretreatment of 200°C for 10 min at neutral pH. [ABSTRACT FROM AUTHOR]