Abstract Background Mild hyperglycaemia is associated with increased birth weight but association with other neonatal outcomes is controversial. We aimed to study neonatal outcomes in untreated mild hyperglycaemia using different oral glucose tolerance test (OGTT) thresholds. Methods This register-based study included all (n = 4,939) singleton pregnant women participating a 75 g 2-hour OGTT in six delivery hospitals in Finland in 2009. Finnish diagnostic cut-offs for GDM were fasting ≥ 5.3, 1-hour ≥ 10.0 or 2-hour glucose ≥ 8.6 mmol/L. Women who did not meet these criteria but met the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting 5.1–5.2 mmol/L and/or 2-hour glucose 8.5 mmol/L, n = 509) or the National Institute for Health and Clinical Excellence (NICE) criteria (2-hour glucose 7.8–8.5 mmol/L, n = 166) were considered as mild untreated hyperglycaemia. Women who met both the Finnish criteria and the IADPSG or the NICE criteria were considered as treated GDM groups (n = 1292 and n = 612, respectively). Untreated mild hyperglycemia groups and treated GDM groups were compared to controls, who were normoglycemic according to all criteria (fasting < 5.1 mmol/L, 1-hour glucose < 10.0 mmol/L and 2-hour glucose < 8.5 mmol/L, n = 3031). The primary outcome - a composite of adverse neonatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality – was analysed using multivariate logistic regression. Results Compared to controls, the risk for the adverse neonatal outcome was not increased in mild hyperglycemia according to the IADPSG criteria (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 0.71–1.44) or the NICE criteria (aOR: 1.05, 95% CI: 0.60–1.85). Discussion The risk of adverse neonatal outcomes was not increased in mild untreated hyperglycaemia. The OGTT cut-offs of 5.3 mmol/L at fasting and 8.6 mmol/L at 2 hours seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes.

Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

Francisella tularensis is a Gram-negative bacteria, that may cause a zoonotic disease, tularemia. Here, we describe a patient case, where a previously healthy young woman in Northern Finland contacted health care because of fever and headache. Due to the symptoms and lack of further diagnostic tools in primary health care, she was transferred to University Hospital (UH) where ampicillin and ceftriaxone was given empirically. A cerebrospinal fluid sample (CSF) was drawn showing small Gram-negative rods that grew on chocolate agar after 2 days of incubation. Matrix-assisted laser-desorption-ionization time of-flight (Maldi-tof) did not provide identification, but the bacteria was interpreted as sensitive to ciprofloxacin and the treatment was changed to ciprofloxacin. During the time the patient was infected, there were several positive tularemia samples found in the area. Therefore, an in house tularemia nucleic acid method (PCR) was used on the bacterial culture. Additionally, 16S rDNA sequencing was performed and these methods identified the bacteria as F. tularensis. Fortunately, the patient recovered completely with ciprofloxacin and was discharged without any complications. Our case underlines the need to understand the limits of specific diagnostic methods, such as Maldi-tof, used in clinical laboratory settings. It also highlights the need of both clinicians and laboratory staff to be aware of the many clinical presentations of tularemia when working in an endemic area.

Les scénaristes de séries télévisées constituent en France un groupe professionnel en voie de visibilité mais toujours en quête de reconnaissance. À partir d’une enquête par entretiens, cet article étudie la constitution de la profession de scénaristes par l’identification de générations de scénaristes qui se distinguent, s’opposent ou se rapprochent par leur conception du métier, leurs pratiques, le déroulement de leur carrière et le moment de leur entrée dans la profession. L’article met ainsi en lumière des vagues successives d’auteur·e·s entrant sur le marché de l’écriture de fiction. Nous partons des travaux fondateurs de Dominique Pasquier (1995) pour montrer comment ce que nous appelons la génération des auteurs de l’industrialisation de la télévision succède, dans les années 1990, à celle des pionniers de l’époque de l’ORTF. Au milieu des années 2000, une nouvelle vague de scénaristes construit une identité professionnelle en opposition avec ses prédécesseurs et s’organise en collectifs : c’est la génération du collectif, qui instaure de nouvelles pratiques de compagnonnage. Enfin, nous discutons des effets de l’ouverture de formations spécifiques à l’écriture sur l’arrivée d’auteur·e·s « juniors », revendiquant leur filiation avec la génération du collectif et que nous appelons les « héritier·e·s ». .

In this cohort study of 800 children attending a pediatric emergency department at Oulu University Hospital, Finland with fever or respiratory symptoms, the cycle threshold values of point-of-care multiplex polymerase chain reaction testing for respiratory viruses were not associated with hospitalization, respiratory support, or need for intensive care.

Ceramides contribute to the development of type 2 diabetes but it is uncertain whether they predict gestational diabetes (GDM). In this multicentre case-control study including 1040 women with GDM and 958 non-diabetic controls, early pregnancy (mean 10.7 gestational weeks) concentrations of four ceramides-Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)-were determined by a validated mass-spectrometric method from biobanked serum samples. Traditional lipids including total cholesterol, LDL, HDL and triglycerides were measured. Logistic and linear regression and the LASSO logistic regression wereusedto analyse lipids and clinical risk factors in the prediction of GDM. The concentrations of four targeted ceramides and total cholesterol, LDL and triglycerides were higher and HDL was lower among womenwith subsequent GDM than among controls.After adjustments, Cer(d18:1/24:0), triglycerides and LDL were independent predictors ofGDM, women in their highest quartile had 1.44-fold (95% CI 1.07-1.95), 2.17-fold (95% CI 1.57-3.00) and 1.63-fold (95% CI 1.19-2.24) odds for GDM when compared to their lowest quartiles, respectively. In the LASSO regression modelling ceramides did not appear to markedly improve the predictive performance for GDM alongside with clinical risk factors and triglycerides. However, their adverse alterations highlight the extent of metabolic disturbances involved in GDM.

Copy number variants (CNVs) are a major source of genetic variation and can disrupt genes or affect gene dosage. They are known to be causal or underlie predisposition to various diseases. However, the role of CNVs in inherited breast cancer susceptibility has not been thoroughly investigated. To address this, we performed whole-exome sequencing based analysis of rare CNVs in 98 high-risk Northern Finnish breast cancer cases. After filtering, selected candidate alleles were validated and characterized with a combination of orthogonal methods, including PCR-based approaches, optical genome mapping and long-read sequencing. This revealed three recurrent alterations: a 31 kb deletion co-occurring with a retrotransposon insertion (delins) in RAD52, a 13.4 kb deletion in HSD17B14 and a 64 kb partial duplication of RAD51C. Notably, all these genes encode proteins involved in pathways previously identified as essential for breast cancer development. Variants were genotyped in geographically matched cases and controls (altogether 278 hereditary and 1983 unselected breast cancer cases, and 1229 controls). The RAD52 delins and HSD17B14 deletion both showed significant enrichment among cases with indications of hereditary disease susceptibility. RAD52 delins was identified in 7/278 cases (2.5%, P = 0.034, OR = 2.86, 95% CI = 1.10-7.45) and HSD17B14 deletion in 8/278 cases (2.9%, P = 0.014, OR = 3.28, 95% CI = 1.31-8.23), the frequency of both variants in the controls being 11/1229 (0.9%). This suggests a role for RAD52 and HSD17B14 in hereditary breast cancer susceptibility. The RAD51C duplication was very rare, identified only in 2/278 of hereditary cases and 2/1229 controls (P = 0.157, OR = 4.45, 95% CI = 0.62-31.70). The identification of recurrent CNVs in these genes, and especially the relatively high frequency of RAD52 and HSD17B14 alterations in the Finnish population, highlights the importance of studying CNVs alongside single nucleotide variants when searching for genetic factors underlying hereditary disease predisposition.

Abstract Francisella tularensis is a gram negative bacteria, that may cause a zoonotic disease, tularemia. We describe here a patient case, where previously healthy young woman in Northern Finland contacted primary/occupational health care as she had fever and headache. Due to the symptoms and lack of further diagnostic tools in the primary health care, the patient was transferred to University Hospital (UH). There she received empirically ampicillin and cetriaxone. In the UH the cerebrospinal fluid sample (CSF) was drawn and subsequently scarce growth of small gram negative bacteria was observed. Maldi-tof did not provide identification, but the bacteria was found to be sensitive to ciprofloxacin with disk diffusion method and subsequently the treatment was redirected to ciprofloxacin. During the time patient was infected, there were several positive tularemia samples found in the area. Therefore, in house tularemia nucleic acid method (PCR) was used on the growing bacteria. Additionally, 16S rDNA sequencing was performed and these methods identified the bacteria as F. tularensis spp. holarctica. Fortunately, the patient recovered completely with ciprofloxacin and was discharged without any further complications or permanent side effects. Our case underlines the need to fully understand the limits of specific diagnostic methods such as Maldi-tof used in clinical laboratory settings.

Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]. Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.

Cytokine-mediated mast cell regulation enables precise optimization of their own pro-inflammatory cytokine production. During allergic inflammation, Interleukin(IL)-4 regulates mast cell functions, tissue-homing and proliferation, but the direct role of closely related IL-13 for mast cell activation remains unclear. Previous work has shown that mast cells are potent IL-13 producers, but here we show that mouse mast cells do not directly respond to IL-13 by Stat6 activation, as they do not express measurable amount of IL-13Rα1 mRNA. Consequently, IL-4 responses are mediated via type I IL-4R (IL-4/IL4Rα/γC) and IL-4-induced Stat6 activation is abolished in γC deficient mast cells. Type II IL-4R deficiency (IL-13Rα1 KO) has no effect on IL-4-induced Stat6 activation. In basophils, both IL-4 and IL-13 induce Stat6 activation in WT and γC deficient cells, while in type II IL-4R deficient basophils IL-4 signaling is impaired at low ligand concentration. Thus, mast cell and basophil sensitivity to IL-4/IL-13 is different and in mast cells, lack of IL-13Rα1 expression likely explains their unresponsiveness to IL-13.