Impact of pregestational obesity on perinatal complications: update in a Latin American cohort.

OBJECTIVES: While the association between pregestational obesity and perinatal complications has been established, it is necessary to update the current understanding of its impact on maternal and foetal health due to its growing prevalence. Thus, this study aimed to investigate the association between pregestational obesity with the leading perinatal complications during the last 6 years. STUDY DESIGN: A cross-sectional study was performed in San Felipe, Chile. Anonymised data of 11,197 deliveries that occurred between 2015 and 2021 were included. METHODS: Pregestational body mass index was defined according to the World Health Organisation during the first trimester of pregnancy. The association between pregestational obesity and perinatal complications was analysed by calculating the odds ratio (OR), which was adjusted for confounding variables. Statistical differences were considered with a P-value of <0.05. RESULTS: The prevalence of pregestational obesity was 30.1%. Pregestational obesity was related to a high incidence of perinatal complications (≥3 complications; P < 0.0001). The main perinatal complications were caesarean section, large for gestational age (LGA), gestational diabetes (GD), macrosomia, hypertensive disorders of pregnancy (HDP), premature rupture of membranes (PROM), intrauterine growth restriction, and failed induction. Pregestational obesity was shown to be a risk factor for macrosomia (OR: 2.3 [95% confidence interval {95% CI}: 2.0-2.8]), GD (OR: 1.9 [95% CI: 1.6-2.1]), HDP (OR: 1.8 [95% CI: 1.5-2.1]), LGA (OR: 1.6 [95% CI: 1.5-1.8]), failed induction (OR: 1.4 [95% CI: 1.0-1.8]), PROM (OR: 1.3 [95% CI: 1.1-1.6]), and caesarean section (OR: 1.3 [95% CI: 1.2-1.4]). CONCLUSIONS: Pregestational obesity has been shown to be a critical risk factor for the main perinatal complications in the study population. Pregestational advice is imperative not only in preventing pregestational obesity but also in the mitigation of critical perinatal complications once they arise.

Immunosuppression and resultant viral persistence by specific viral targeting of dendritic cells.

Among cells of the immune system, CD11c(+) and DEC-205(+) splenic dendritic cells primarily express the cellular receptor (alpha-dystroglycan [alpha-DG]) for lymphocytic choriomeningitis virus (LCMV). By selection, strains and variants of LCMV that bind alpha-DG with high affinity are associated with virus replication in the white pulp, show preferential replication in a majority of CD11c(+) and DEC-205(+) cells, cause immunosuppression, and establish a persistent infection. In contrast, viral strains and variants that bind with low affinity to alpha-DG are associated with viral replication in the red pulp, display minimal replication in CD11c(+) and DEC-205(+) cells, and generate a robust anti-LCMV cytotoxic T lymphocyte response that clears the virus infection. Differences in binding affinities can be mapped to a single amino acid change in the viral glycoprotein 1 ligand that binds to alpha-DG. These findings indicate that receptor-virus interaction on dendritic cells in vivo can be an essential step in the initiation of virus-induced immunosuppression and viral persistence.

Constitutive beta cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes.

To analyze the function of the Th1-promoting cytokine IL-12 in vivo, we generated transgenic (tg) mice (RIP-IL12 mice) whose pancreatic beta cells constitutively express bioactive IL-12 or one of its components, p35 or p40. In contrast to non-tg littermates or single-tg RIP-p35 and RIP-p40 mice, RIP-IL12 mice developed a marked pancreatic infiltration of lymphocytes and macrophages, mainly around islets. Expression of bioactive IL-12 primarily upregulated transcript levels of IFN-inducible protein-10 (IP-10), RANTES, IFN-gamma, and TNF-alpha in the pancreas. Despite the substantial recruitment of mononuclear cells, no biochemical or clinical disease was evident in the exocrine or endocrine pancreas. Coexpression of lymphocytic choriomeningitis virus (LCMV) proteins with IL-12 in the beta cells failed to spontaneously activate or expand antigen-specific anti-self/viral T cells in uninfected tg animals. However, when RIP-IL12 x RIP-LCMV tg mice were infected with LCMV, antigen-specific anti-self/viral T cells were induced, which led to an acceleration in the kinetics and severity of insulin-dependent diabetes mellitus (IDDM). Thus, the ectopic expression of IL-12 does not spontaneously break tolerance and activate antigen-specific T cells in the periphery, but it does worsen ongoing autoimmune disease.

Fate map and cell lineage relationships of thoracic and abdominal mesodermal anlagen in Drosophila melanogaster.

We have examined the cell lineage of larval and imaginal precursors of the mesodermal anlage between 10% and 60% egg length (EL) by homotopic single-cell transplantations at the blastoderm stage. Clones in the larval somatic muscles and in the fat body were derived from transplantations everywhere between 10% and 60% EL along the ventral side of the embryo. Clones frequently overlap these tissues and can extend over a maximum of four segments in the larval somatic muscles or over two morphologically-distinct parts in the fat body. Clones in the gonadal mesoderm overlap with other mesodermal derivatives and exhibit different mitotic behaviour in the two sexes. We present a blastoderm fate map for the fat body, the larval somatic muscles and the gonadal mesoderm. Clones in the imaginal muscle precursors of the abdomen, as well as of the thorax, always show a common cell lineage with larval somatic muscles and partly with other mesodermal tissues. These clones of imaginal derivatives are always found within a single segment, while the overlapping clone parts in the larval somatic muscles can label up to three segments.

Adepithelial cells in Drosophila melanogaster: origin and cell lineage.

We have analysed the cell lineage relationships between larval and imaginal mesodermal primordia at the blastoderm stage by homotopic single cell transplantations. The primordia of adepithelial cells, the precursors of adult thoracic muscles, are restricted to the region from 50 to 65% egg length within the ventrally located mesodermal anlage. Clones of adepithelial cells always show a common cell lineage with larval muscles and in some cases additionally with larval fat body. This proves that at the blastoderm stage the determination of larval vs. imaginal mesodermal primordia has not yet taken place. Larval somatic muscle clones, in contrast to clones in the ectoderm, can overlap several segments, whereas clones of adepithelial cells are always restricted to imaginal discs of one segment.

Essential genes for myoblast fusion in Drosophila embryogenesis.

In Drosophila, as in vertebrates, each muscle is a syncytium and arises from mesodermal cells by successive fusion. This requires cell-cell recognition, alignment, formation of prefusion complexes, followed by electron-dense plaques and membrane breakdown. Because muscle development in Drosophila is rapid and well-documented, it has been possible to identify several genes essential for fusion. Molecular analysis of two of these genes revealed the importance of cytoplasmic components. One of these, Myoblast city, is expressed in several tissues and is homologous to the mammalian protein DOCK180. Myoblast city is presumably involved in cell recognition and cell adhesion. Blown fuse, the second cytoplasmic component, is selectively expressed in the mesoderm and essential in order to proceed from the prefusion complex to electron-dense plaques at opposed membranes between adjacent myoblasts. The rolling stone gene is transiently expressed during myoblast fusion. The Rost protein is located in the membrane and thus might be a key component for cell recognition. The molecular characterization of further genes relevant for fusion such as singles bar and sticks and stones will help to elucidate the mechanism of myoblast fusion in Drosophila.

Larval and imaginal pathways in early development of Drosophila.

In holometabolous development, higher insects have two different life forms, the larva and the imago. Both larval and imaginal cells are derived from cells of the blastoderm stage. After the final embryonic wave of mitosis, however, only the imaginal cells remain diploid, proliferate massively and do not differentiate until metamorphosis. The separation of these two pathways was described by many authors as a fundamental process that must take place at a very early stage of development, most probably the blastoderm stage. Mainly by using single cell transplantations at the blastoderm or early gastrula stages, respectively, we found common cell lineages between larval and imaginal structures by clones overlapping in the ectoderm (i.e. larval epidermal cells and imaginal discs within a segment, or larval and imaginal salivary gland cells), the mesoderm (i.e. larval somatic muscles and adepithelial cells), and the endoderm (i.e. larval and imaginal midgut cells). From these findings we conclude that it seems to be a principle in Drosophila embryogenesis that the separation of larval and imaginal pathways is postponed to a later developmental stage.

The complex of oriC DNA with the DnaA initiator protein.

We describe several experimental approaches relating to the early steps in the initiation of DNA replication at oriC. 1) A matrix is given which enables calculatation of the relative affinity of DnaA boxes for DnaA protein; 2) base changes within single Dna A boxes in oriC have little effect on oriC function; 3) mutations which change the distance between DnaA boxes inactivate oriC, but changes by one helical turn (+ and -) result in near wild-type oriC activity; 4) a Fis binding site was located at oriC coordinates 206-220; 5) KMnO4 probing demonstrates Dna-A-dependent unwinding in the left part of oriC in vivo and in vitro.

MR imaging of infections of the cervical spine.

Spine infections are serious clinical conditions that carry high morbidity and mortality rates. Cervical spine infections usually require a more aggressive medical and surgical approach than infections in the rest of the spine. Often, more than one anatomic structure or compartment becomes affected. Topics discussed in this article include incidence and predisposing factors of spine infections, types of micro-organisms involved in several disease conditions, pathophysiology and clinical manifestations, and imaging findings and MR imaging features.

[Cystectomy in elderly patients: analysis of complications using the Clavien-Dindo classification]. / Die Zystektomie im Alter : Komplikationsanalyse unter Anwendung der Clavien-Dindo-Klassifikation.

Radical cystectomy (RC) represents the gold standard in the treatment of muscle invasive urothelial cancer of the bladder. Due to improvements in operation techniques and perioperative care it has become a good and safe procedure even in elderly patients. In recent years the Clavien-Dindo classification has been frequently used for complication assessment in urological research. The Charlson comorbidity index without age correction can be used in treatment planning for RC to identify patients at risk.

[Bladder dysfunction caused by a large presacral retention mucocele]. / Blasenfunktionsstörung in Folge einer grossen präsakralen Retentionsmukozele.

Large pelvic masses can displace the urinary bladder and cause bladder dysfunction with various symptoms. We report the case of a 42-year-old man who described a feeling of reduced urinary stream and bladder filling and residual urine since his youth. After various unsuccessful conservative treatments, the patient was evaluated by our neuro-urologic department. The diagnostic workup revealed a large cystic mass that displaced the urinary bladder. Histopathological examination showed a retention mucocele (the patient had been surgically treated for connatal anal atresia). The lesion was surgically excised.

Approach to risk reduction in manufacturing firms in Australia.

A survey of the 100 largest manufacturing firms in Australia has revealed that there is a lack of emphasis on controlling the incidence of high severity injuries and diseases. In a considerable number of organizations, there appears to be a reliance on the attitude of employees and safety training to control risk. There seems to be a lack of knowledge among the respondents of information sources which can be used to assess both risk and proposed control measures. The results suggest that Robens type legislation may be of limited utility in controlling risk in the workplace and a more definitive approach to identifying hazards and instituting appropriate control measures should be provided to organizations.

Pathological changes in the islet milieu precede infiltration of islets and destruction of beta-cells by autoreactive lymphocytes in a transgenic model of virus-induced IDDM.

RIP-LCMV transgenic mice that express the viral glycoprotein (GP) or nucleoprotein (NP) from lymphocytic choriomeningitis virus (LCMV) under control of the rat insulin promoter (RIP) in pancreatic beta-cells develop autoimmune diabetes (IDDM) after infection with LCMV. Previous reports have described that the viral infection activates naive, potentially autoreactive CD8+ cytotoxic T-lymphocytes (CTL) that are present in the periphery of these mice, thus leading to the breaking of immunological unresponsiveness to the viral self-antigen expressed on beta-cells. However, we find that adoptive transfer of such CTL that were active in vitro and in vivo into uninfected RIP-LCMV recipients rarely resulted in hyperglycemia nor in insulitis, despite their ability to home to the islets and induce peri-insulitis. These observations indicated that, in addition to activated autoreactive lymphocytes, other factor(s) were required for beta-cell destruction. The present study shows that upregulation of MHC class II molecules associated with the attraction/activation of antigen presenting cells (APCs) to the islets occurs as soon as 2 days after LCMV inoculation of transgenic mice, clearly before CD4+ and CD8+ lymphocytes are found entering the islets (days 6 and 7 after LCMV inoculation). In contrast, although some MHC class II upregulation is also found in islets of non-transgenic mice 2-4 days after LCMV infection, no insulitis or IDDM develops and MHC is downregulated to normal (pre-infection) levels by day 7-10 in these mice. Associated with the activation of APCs and MHC upregulation observed in transgenic mice, viral (LCMV) infection of islets was detectable 2 days post-viral inoculation in some mice. Thus, beta-cell destruction by activated autoreactive lymphocytes is a multifactorial process that is likely to require changes within the islet milieu or dysfunction of islets.