Deletion of protein tyrosine phosphatase SHP-1 restores SUMOylation of podocin and reverses the progression of diabetic kidney disease.

Both clinical and experimental data suggest that podocyte injury is involved in the onset and progression of diabetic kidney disease (DKD). Although the mechanisms underlying the development of podocyte loss are not completely understood, critical structural proteins such as podocin play a major role in podocyte survival and function. We have reported that the protein tyrosine phosphatase SHP-1 expression increased in podocytes of diabetic mice and glomeruli of patients with diabetes. However, the in vivo contribution of SHP-1 in podocytes is unknown. Conditional podocyte-specific SHP-1-deficient mice (Podo-SHP-1-/-) were generated to evaluate the impact of SHP-1 deletion at four weeks of age (early) prior to the onset of diabetes and after 20 weeks (late) of diabetes (DM; Ins2+/C96Y) on kidney function (albuminuria and glomerular filtration rate) and kidney pathology. Ablation of the SHP-1 gene specifically in podocytes prevented and even reversed the elevated albumin/creatinine ratio, glomerular filtration rate progression, mesangial cell expansion, glomerular hypertrophy, glomerular basement membrane thickening and podocyte foot process effacement induced by diabetes. Moreover, podocyte-specific deletion of SHP-1 at an early and late stage prevented diabetes-induced expression of collagen IV, fibronectin, transforming growth factor-ß, transforming protein RhoA, and serine/threonine kinase ROCK1, whereas it restored nephrin, podocin and cation channel TRPC6 expression. Mass spectrometry analysis revealed that SHP-1 reduced SUMO2 post-translational modification of podocin while podocyte-specific deletion of SHP-1 preserved slit diaphragm protein complexes in the diabetic context. Thus, our data uncovered a new role of SHP-1 in the regulation of cytoskeleton dynamics and slit diaphragm protein expression/stability, and its inhibition preserved podocyte function preventing DKD progression.

Reduction of DUSP4 contributes to podocytes oxidative stress, insulin resistance and diabetic nephropathy.

Podocytes are insulin-sensitive cells, and their loss is critical in diabetic nephropathy (DN) progression that could lead to end-stage kidney disease. We have previously shown that decreased DUSP4 expression caused elevated JNK phosphorylation in the diabetic kidney and worsened DN characteristics. Yet, the role of DUSP4 in diabetic podocyte insulin resistance and the progression of DN remains unclear. Here, we report that HG-exposed podocytes exhibited reduced DUSP4 expression, increased phosphorylation of JNK and serine 307 of IRS1 as well as Nox4 expression, while decreasing insulin signaling actions. DUSP4 overexpression, JNK and Nox1/4 inhibition prevented HG-induced serine 307 phosphorylation of IRS1 and restored insulin actions. Diabetic mice showed renal dysfunction and insulin resistance, characteristics that were exacerbated in diabetic DUSP4 deficient mice due to Nox1/4 upregulation. Thus, our results demonstrated that diabetes-induced reduction of DUSP4 leads to JNK activation and elevated Nox4 expression, which contributes to podocyte dysfunction, insulin resistance and progression of DN.

Guideline No. 426: Hypertensive Disorders of Pregnancy: Diagnosis, Prediction, Prevention, and Management.

OBJECTIVE: This guideline was developed by maternity care providers from obstetrics and internal medicine. It reviews the diagnosis, evaluation, and management of the hypertensive disorders of pregnancy (HDPs), the prediction and prevention of preeclampsia, and the postpartum care of women with a previous HDP. TARGET POPULATION: Pregnant women. BENEFITS, HARMS, AND COSTS: Implementation of the recommendations in these guidelines may reduce the incidence of the HDPs, particularly preeclampsia, and associated adverse outcomes. EVIDENCE: A comprehensive literature review was updated to December 2020, following the same methods as for previous Society of Obstetricians and Gynaecologists of Canada (SOGC) HDP guidelines, and references were restricted to English or French. To support recommendations for therapies, we prioritized randomized controlled trials and systematic reviews (if available), and evaluated substantive clinical outcomes for mothers and babies. VALIDATION METHODS: The authors agreed on the content and recommendations through consensus and responded to peer review by the SOGC Maternal Fetal Medicine Committee. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, along with the option of designating a recommendation as a "good practice point." See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations).The Board of the SOGC approved the final draft for publication. INTENDED USERS: All health care providers (obstetricians, family doctors, midwives, nurses, and anesthesiologists) who provide care to women before, during, or after pregnancy.

Directive clinique no 426 : Troubles hypertensifs de la grossesse : Diagnostic, prédiction, prévention et prise en charge.

OBJECTIF: La présente directive a été élaborée par des fournisseurs de soins de maternité en obstétrique et en médecine interne. Elle aborde le diagnostic, l'évaluation et la prise en charge des troubles hypertensifs de la grossesse, la prédiction et la prévention de la prééclampsie ainsi que les soins post-partum des femmes avec antécédent de trouble hypertensif de la grossesse. POPULATION CIBLE: Femmes enceintes. BéNéFICES, RISQUES ET COûTS: La mise en œuvre des recommandations de la présente directive devrait réduire l'incidence des troubles hypertensifs de la grossesse, en particulier la prééclampsie, et des issues défavorables associées. DONNéES PROBANTES: La revue exhaustive de la littérature a été mise à jour en tenant compte des nouvelles données probantes jusqu'en décembre 2020 et en suivant la même méthodologie que pour la précédente directive de la Société des obstétriciens et gynécologues du Canada (SOGC) sur les troubles hypertensifs de la grossesse. La recherche s'est limitée aux articles publiés en anglais ou en français. Les recommandations relatives aux traitements s'appuient d'abord sur les essais cliniques randomisés et les revues systématiques (lorsque disponibles), ainsi que sur l'évaluation des résultats cliniques substantiels chez les mères et les bébés. MéTHODES DE VALIDATION: Les auteurs se sont entendus sur le contenu et les recommandations par consensus et ont répondu à l'examen par les pairs du comité de médecine fœto-maternelle de la SOGC. Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique d'évaluation, de développement et d'évaluation (GRADE) et se sont gardé l'option de désigner certaines recommandations par la mention « bonne pratique ¼. Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). Le conseil d'administration de la SOGC a approuvé la version définitive aux fins de publication. PROFESSIONNELS CIBLES: Tous les fournisseurs de soins de santé (obstétriciens, médecins de famille, sages-femmes, infirmières et anesthésistes) qui prodiguent des soins aux femmes avant, pendant ou après la grossesse.

Impact of an Educational Pamphlet on Knowledge About Health Risks After Hypertensive Disorders of Pregnancy: A Randomized Trial.

OBJECTIVE: To evaluate patients' knowledge, risk perception, and anxiety about future health risks after an episode of hypertensive disorder of pregnancy (HDP), as well as their satisfaction with an educational pamphlet. METHODS: From January 2016 to June 2017, participants were randomly assigned to one of 2 groups and asked to complete questionnaire #1 (demographics, knowledge, risk perception, anxiety, and satisfaction) after receiving medical counselling at the HDP postpartum clinic. Participants in the intervention group then received the educational pamphlet. One month later, both groups completed the questionnaire again (questionnaire #2). The primary outcome of this study was improvement in the global knowledge score at 1 month, reflecting improved understanding of the health risks of HDP. Secondary outcomes included retention of information, risk perception, satisfaction, and anxiety level. RESULTS: Of 137 eligible women, 57 were randomly assigned to the intervention group and 56, to the control group. Participants in both groups had similar baseline characteristics. Thirteen percent of participants did not complete questionnaire #2. The knowledge score was higher in the intervention group than the control group at 1 month, (88.2%; 95% confidence interval [CI] 26.37-28.32 and 71.3%; 95% CI 20.78-23.45, respectively [P <0.0001]). No difference was seen in anxiety level between the groups (4.0 ± 1.00 vs. 3.8 ± 0.92; P = 0.6746). The intervention group was highly satisfied with the medical counselling they received (5.5 ± 0.84 out 6) and with the pamphlet (5.6 ± 0.66 out 6). CONCLUSION: The educational pamphlet increased women's knowledge about future health risks of HDP without increasing anxiety and it may be helpful in promoting lifestyle changes necessary to modify these risks.

Extended Linkers Improve the Detection of Protein-protein Interactions (PPIs) by Dihydrofolate Reductase Protein-fragment Complementation Assay (DHFR PCA) in Living Cells.

Understanding the function of cellular systems requires describing how proteins assemble with each other into transient and stable complexes and to determine their spatial relationships. Among the tools available to perform these analyses on a large scale is Protein-fragment Complementation Assay based on the dihydrofolate reductase (DHFR PCA). Here we test how longer linkers between the fusion proteins and the reporter fragments affect the performance of this assay. We investigate the architecture of the RNA polymerases, the proteasome and the conserved oligomeric Golgi (COG) complexes in living cells and performed large-scale screens with these extended linkers. We show that longer linkers significantly improve the detection of protein-protein interactions and allow to measure interactions further in space than the standard ones. We identify new interactions, for instance between the retromer complex and proteins related to autophagy and endocytosis. Longer linkers thus contribute an enhanced additional tool to the existing toolsets for the detection and measurements of protein-protein interactions and protein proximity in living cells.

Albumin/Creatinine Ratio for the Detection of Significant Proteinuria of Preeclampsia in Hospitalized Hypertensive Women.

OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy associated with proteinuria detected by 24-hour urine collection (≥0.3 g/24 h) or protein/creatinine ratio (≥30 mg/mmol). The albumin/creatinine ratio (ACR) is used outside pregnancy to detect abnormal amounts of albumin in the urine, but there is little data on its value in pregnancy. Our objective was to determine the diagnostic threshold for ACR to detect significant proteinuria in women investigated for preeclampsia. METHODS: A prospective observational study involving 99 hypertensive women (≥140/90 mm Hg) over 20 weeks gestation who were hospitalized at 2 Canadian tertiary centres. A 24-hour urine collection and a morning urine sample were collected. The optimal ACR threshold was determined by a receiver operating characteristic (ROC) curve using the 24-hour collection as the reference test; sensitivity and specificity analyses were performed. Maternal and perinatal characteristics were extracted from medical records. RESULTS: Of the 87 women who had completed urine collection, 74 (85%) had an initial diagnosis of preeclampsia and 63 (72%) had significant proteinuria confirmed by 24-hour collection. The area under the morning ROC curve was 0.92 (95% CI 0.86-0.98) and the optimal threshold obtained for the ACR was 9 mg/mmol, with a sensitivity and specificity of 84% (95% CI 73-92) and 88% (95% CI 68-97), respectively. CONCLUSION: Our results suggest that an ACR threshold of 9 mg/mmol on a morning urine sample can be used to detect significant proteinuria of preeclampsia in hospitalized hypertensive women.

Pre-eclampsia Educational Tool Impact on Knowledge, Anxiety, and Satisfaction in Pregnant Women: A Randomized Trial.

OBJECTIVE: This study aimed to evaluate the impact of educational tools concerning pre-eclampsia on knowledge, anxiety, and women's satisfaction. METHODS: The investigators conducted a randomized controlled trial from March to July 2014 at the Centre Hospitalier Universitaire de Sherbrooke (Sherbrooke, QC) by comparing ambulatory pregnant women (20-32 weeks of gestation) who were receiving educational tools on pre-eclampsia with control patients who received routine care. Tools consisted of an informative pamphlet, a video, and a pictographic magnet, all validated by a multidisciplinary team. The primary outcome was global knowledge (number of correct answers on 35 items) about the disease after 1 month, as assessed by questionnaire. Secondary outcomes included anxiety regarding pre-eclampsia and satisfaction concerning the different tools (a 1-6 Likert scale was used). RESULTS: Among 362 pregnant women approached for the research, 269 were randomized. After 1 month, 247 questionnaires (92%) were filled and analyzed: 122 from the control group and 125 from the intervention group. Baseline characteristics were similar between the groups. Patients who received the tools scored significantly higher on global knowledge (70.1% ± 19.2% compared with 51.1% ± 23.4%; mean difference of 19.0%; P < 0.001). Anxiety scores regarding pre-eclampsia were similar between the groups, with a mean of 2.40 out of 6 for the control group and 2.53 out of 6 for the intervention group (equivalence test, P < 0.001). High score levels of satisfaction for the pamphlet and video were found: 5.1 out of 6 and 5.2 out of 6, respectively. CONCLUSION: These well-received educational tools for pregnant women increased their knowledge about pre-eclampsia without increasing their anxiety about it. Women reported the highest satisfaction for the tools.

Standing chromosomal variation in Lake Whitefish species pairs: the role of historical contingency and relevance for speciation.

The role of chromosome changes in speciation remains a debated topic, although demographic conditions associated with divergence should promote their appearance. We tested a potential relationship between chromosome changes and speciation by studying two Lake Whitefish (Coregonus clupeaformis) lineages that recently colonized postglacial lakes following allopatry. A dwarf limnetic species evolved repeatedly from the normal benthic species, becoming reproductively isolated. Lake Whitefish hybrids experience mitotic and meiotic instability, which may result from structurally divergent chromosomes. Motivated by this observation, we test the hypothesis that chromosome organization differs between Lake Whitefish species pairs using cytogenetics. While chromosome and fundamental numbers are conserved between the species (2n = 80, NF = 98), we observe extensive polymorphism of subtle karyotype traits. We describe intrachromosomal differences associated with heterochromatin and repetitive DNA, and test for parallelism among three sympatric species pairs. Multivariate analyses support the hypothesis that differentiation at the level of subchromosomal markers mostly appeared during allopatry. Yet we find no evidence for parallelism between species pairs among lakes, consistent with colonization effect or postcolonization differentiation. The reported intrachromosomal polymorphisms do not appear to play a central role in driving adaptive divergence between normal and dwarf Lake Whitefish. We discuss how chromosomal differentiation in the Lake Whitefish system may contribute to the destabilization of mitotic and meiotic chromosome segregation in hybrids, as documented previously. The chromosome structures detected here are still difficult to sequence and assemble, demonstrating the value of cytogenetics as a complementary approach to understand the genomic bases of speciation.

History repeats itself: genomic divergence in copepods.

Press stop, erase everything from now till some arbitrary time in the past and start recording life as it evolves once again. Would you see the same tape of life playing itself over and over, or would a different story unfold every time? The late Steven Jay Gould called this experiment replaying the tape of life and argued that any replay of the tape would lead evolution down a pathway radically different from the road actually taken (Gould 1989). This thought experiment has puzzled evolutionary biologists for a long time: how repeatable are evolutionary events? And if history does indeed repeat itself, what are the factors that may help us predict the path taken? A powerful means to address these questions at a small evolutionary scale is to study closely related populations that have evolved independently, under similar environmental conditions. This is precisely what Pereira et al. (2016) set out to do using marine copepods Tigriopus californicus, and present their results in this issue of Molecular Ecology. They show that evolution can be repeatable and even partly predictable, at least at the molecular level. As expected from theory, patterns of divergence were shaped by natural selection. At the same time, strong genetic drift due to small population sizes also constrained evolution down a similar evolutionary road, and probably contributed to repeatable patterns of genomic divergence.

RNA-seq reveals transcriptomic shock involving transposable elements reactivation in hybrids of young lake whitefish species.

Identifying the molecular basis of reproductive isolation among diverging lineages represents an essential step toward understanding speciation in natural populations. Postzygotic barriers can lead to hybrid breakdown, a syndrome that has been documented in several systems, potentially involving the reactivation of transposable elements. In northeastern North America, two lake whitefish lineages have repeatedly colonized postglacial lakes ~12,000 years ago, and a dwarf limnetic species has evolved multiple times from the normal benthic species. Reproductive isolation is incomplete between them; viable hybrids can be generated in the laboratory but significant mortality occurs and is associated with a malformed phenotype in backcross embryos, thus revealing a hybrid breakdown syndrome. By means of RNA-seq analyses, the objective of this study was to determine which genes were misregulated in hybrids and rigorously test the hypothesis of transposable element reactivation. We compared the transcriptomic landscape in pure embryos, F1-hybrids, and healthy and malformed backcrosses at the late embryonic stage. Extensive expression differences consistent with previously documented adaptive divergence between pure normal and dwarf embryos were identified for the first time. Pronounced transcriptome-wide deregulation in malformed backcrosses was observed, with over 15% of transcripts differentially expressed in all comparisons, compared with 1.5% between pure parental forms. Convincing evidence of transposable elements and noncoding transcripts reactivation in malformed backcrosses is presented. We propose that hybrid breakdown likely results from extensive genomic incompatibilities, plausibly encompassing transposable elements. Combined with previous studies, these results reveal synergy among many reproductive barriers, thus maintaining divergence between these two young whitefish species.

Reproductive isolation in a nascent species pair is associated with aneuploidy in hybrid offspring.

Speciation may occur when the genomes of two populations accumulate genetic incompatibilities and/or chromosomal rearrangements that prevent inter-breeding in nature. Chromosome stability is critical for survival and faithful transmission of the genome, and hybridization can compromise this. However, the role of chromosomal stability on hybrid incompatibilities has rarely been tested in recently diverged populations. Here, we test for chromosomal instability in hybrids between nascent species, the 'dwarf' and 'normal' lake whitefish (Coregonus clupeaformis). We examined chromosomes in pure embryos, and healthy and malformed backcross embryos. While pure individuals displayed chromosome numbers corresponding to the expected diploid number (2n = 80), healthy backcrosses showed evidence of mitotic instability through an increased variance of chromosome numbers within an individual. In malformed backcrosses, extensive aneuploidy corresponding to multiples of the haploid number (1n = 40, 2n = 80, 3n = 120) was found, suggesting meiotic breakdown in their F1 parent. However, no detectable chromosome rearrangements between parental forms were identified. Genomic instability through aneuploidy thus appears to contribute to reproductive isolation between dwarf and normal lake whitefish, despite their very recent divergence (approx. 15-20 000 generations). Our data suggest that genetic incompatibilities may accumulate early during speciation and limit hybridization between nascent species.

The urinary protein-to-creatinine ratio in Canadian women at risk of preeclampsia: does the time of day of testing matter?

OBJECTIVES: To determine the performance of a protein-to-creatinine ratio threshold of 30 mg/mmol in pregnant women investigated for hypertension according to the time of day of the sample. METHODS: This prospective study included ambulatory pregnant women investigated for hypertensive disorders. A single voided random urine specimen was obtained to determine the protein-to-creatinine ratio, followed immediately by a 24-hour urine collection. Statistical analyses included Spearman correlation, sensitivity, specificity, predictive values, likelihood ratios, and receiver-operator characteristic curves with 95% confidence intervals. A P value < 0.05 was considered statistically significant. RESULTS: Among the 91 specimens analyzed, 47.3% showed significant proteinuria in the 24-hour collection and 33% were first morning samples. The protein-to-creatinine ratio and 24-hour urinary protein excretion were highly correlated (r = 0.92, P < 0.001). The diagnostic accuracy of the protein-to-creatinine ratio threshold of 30 mg/mmol was lower in first morning samples than in samples obtained during the rest of the day, with sensitivity 58% and 90%, specificity 93% and 100%, positive predictive value 88% and 100%, negative predictive value 72% and 92%, positive likelihood ratio 8 and not calculable, and negative likelihood ratio 0.45 and 0.1, respectively. The receiver-operator characteristic area under the curve was 0.94 (95% CI 0.86 to 1) for first morning samples and 1.0 (95% CI 0.99 to 1) for other samples. CONCLUSION: A protein-to-creatinine ratio threshold of 30 mg/mmol reliably identifies significant proteinuria, but its reliability is reduced in first morning samples. Consequently, such samples should not be used for this purpose.

Objectifs : Déterminer le rendement d'un seuil de rapport protéines/créatinine de 30 mg/mmol chez les femmes enceintes qui font l'objet d'une exploration visant l'hypertension, en fonction du moment de la journée où l'échantillon a été prélevé. Méthodes : Cette étude prospective comptait des femmes enceintes ambulatoires qui faisaient l'objet d'une exploration visant des troubles hypertensifs. Un échantillon mictionnel aléatoire unique d'urine a été prélevé aux fins de la détermination du rapport protéines/créatinine, le tout ayant été immédiatement suivi d'un recueil des urines de 24 heures. Parmi les analyses statistiques utilisées, on trouvait la corrélation de Spearman, la sensibilité, la spécificité, les coefficients de prévision, les rapports de vraisemblance et les courbes d'efficacité du récepteur en fonction d'intervalles de confiance à 95 %. Une valeur P < 0,05 a été considérée comme étant significative sur le plan statistique. Résultats : Parmi les 91 échantillons analysés, 47,3 % ont présenté une protéinurie significative dans le cadre du recueil des urines de 24 heures et 33 % étaient issus de la première miction matinale. Le rapport protéines/créatinine et l'excrétion urinaire de protéines sur 24 heures présentaient une forte corrélation (r = 0,92, P < 0,001). La précision diagnostique du seuil de rapport protéines/créatinine de 30 mg/mmol était moins élevée dans le cas des échantillons issus de la première miction matinale que dans celui des échantillons obtenus à d'autres moments de la journée (sensibilité de 58 % et de 90 %, spécificité de 93 % et de 100 %, coefficient de prévision d'un test positif de 88 % et de 100 %, coefficient de prévision d'un test négatif de 72 % et de 92 %, rapport de vraisemblance positif de 8 et incalculable, et rapport de vraisemblance négatif de 0,45 et de 0,1, respectivement). La surface sous la courbe d'efficacité du récepteur était de 0,94 (IC à 95 %, 0,86 - 1) dans le cas des échantillons issus de la première miction matinale et de 1,0 (IC à 95 %, 0,99 - 1) dans le cas des autres échantillons. Conclusion : Bien qu'un seuil de rapport protéines/créatinine de 30 mg/mmol permette d'établir de façon fiable la présence d'une protéinurie significative, sa fiabilité est réduite dans le cas des échantillons issus de la première miction matinale. Par conséquent, de tels échantillons ne devraient pas être utilisés à cette fin.

Uric Acid as a predictor of adverse maternal and perinatal outcomes in women hospitalized with preeclampsia.

OBJECTIVE: Elevated serum uric acid is commonly observed in women with preeclampsia, but its utility in predicting adverse outcomes has recently been disputed. Our goal was to analyze data from a large cohort of women with preeclampsia to determine the utility of serum uric acid in predicting adverse maternal and perinatal outcomes. METHODS: Data were obtained from an ongoing international prospective study of women admitted to hospital with preeclampsia (Pre-eclampsia Integrated Estimate of RiSk). Univariate logistic regression was used to determine the relationship between serum uric acid concentration (both absolute and gestational-age corrected [Z score]) and adverse outcomes (maternal and perinatal). Analyses were conducted to compare cohorts of women with preeclampsia as defined by hypertension and proteinuria versus hypertension and hyperuricemia. RESULTS: Uric acid Z score was associated with adverse perinatal outcome (OR 1.5; 95% CI 1.4 to 1.7) and had a point estimate > 0.7 (area under the curve receiver operating characteristic 0.72; 95% CI 0.69 to 0.74). Serum uric acid concentration also showed a significant association with adverse maternal outcomes, but the point estimate was < 0.7. No significant differences were observed between groups in which preeclampsia was defined by hypertension and proteinuria and by hypertension and hyperuricemia. CONCLUSION: In women admitted to hospital with preeclampsia, the serum uric acid concentration, corrected for gestational age via a Z score, is clinically useful in predicting adverse perinatal outcomes but not maternal outcomes.

Objectif : Bien qu'un taux sérique élevé d'acide urique soit couramment constaté chez les femmes qui présentent une prééclampsie, son utilité pour ce qui est de la prévision des issues indésirables a récemment été remise en question. Nous avions pour objectif d'analyser les données issues d'une importante cohorte de femmes présentant une prééclampsie, afin de déterminer l'utilité du taux sérique d'acide urique pour ce qui est de la prévision des issues indésirables maternelles et périnatales. Méthodes : Les données ont été tirées d'une étude prospective internationale toujours en cours qui porte sur des femmes hospitalisées présentant une prééclampsie (Pre-eclampsia Integrated Estimate of RiSk). Une régression logistique univariée a été utilisée pour déterminer la relation entre la concentration sérique en acide urique (tant absolue que corrigée en fonction de l'âge gestationnel [score Z]) et les issues indésirables (maternelles et périnatales). Des analyses ont été menées pour comparer des cohortes de femmes présentant une prééclampsie définie par l'hypertension et la protéinurie à des cohortes de femmes présentant une prééclampsie définie par l'hypertension et l'hyperuricémie. Résultats : Le score Z quant à l'acide urique était associé à des issues périnatales indésirables (RC, 1,5; IC à 95 %, 1,4 - 1,7) et comptait une estimation ponctuelle > 0,7 (surface sous la courbe de la fonction d'efficacité de l'observateur, 0,72; IC à 95 %, 0,69 - 0,74). Une association significative a également été constatée entre la concentration sérique en acide urique et des issues indésirables maternelles; toutefois, l'estimation ponctuelle était < 0,7. Aucune différence significative n'a été constatée entre les groupes « prééclampsie définie par l'hypertension et la protéinurie ¼ et « prééclampsie définie par l'hypertension et l'hyperuricémie ¼. Conclusion : Bien que la concentration sérique en acide urique (corrigée en fonction de l'âge gestationnel par l'intermédiaire d'un score Z) soit utile sur le plan clinique pour ce qui est de la prévision des issues indésirables périnatales chez les femmes hospitalisées présentant une prééclampsie, elle ne compte pas une utilité semblable en ce qui concerne les issues indésirables maternelles.

Urinary dipstick proteinuria testing: does automated strip analysis offer an advantage over visual testing?

OBJECTIVE: To compare the diagnostic test properties of automated and visually read urine dipstick screening for detection of a random protein:creatinine ratio (PrCr) ≥ 30 mg/mmol. METHODS: Urine samples were collected prospectively from 160 women attending high-risk maternity clinics at a tertiary care facility. Samples were divided into two aliquots; one aliquot was tested using two different urine test strips, one read visually and one by an automated reader. A second aliquot of the same urine was analyzed for urinary protein and creatinine. Performance of visual and automated dipstick results (proteinuria ≥ 1+) were compared for detection of PrCr ≥ 30 mg/mmol using non-dilute urine samples (urinary creatinine ≥ 3 mmol/L). RESULTS: Both urine test strips showed low sensitivity (visual 56.0% and automated 53.8%). Positive likelihood ratios were 15.0 for visual dipstick testing (95% CI 5.9 to 37.9) and 24.6 for automated (95% CI 7.6 to 79.6). Negative likelihood ratios were 0.46 for visual dipstick testing (95% CI 0.29 to 0.71) and 0.47 for automated (95% CI 0.31 to 0.72). CONCLUSION: Automated dipstick testing was not superior to visual testing for detection of proteinuria in pregnant women in a primarily outpatient setting. Sensitivity may depend on the test strips and/or analyzer used.

Objectif : Comparer les propriétés diagnostiques du dépistage automatisé par bandelette réactive urinaire et du dépistage visuel par bandelette réactive urinaire pour ce qui est de la détection d'un rapport protéines/créatinine (PrCr) aléatoire ≥ 30 mg/mmol. Méthodes : Des échantillons d'urine ont été prélevés de façon prospective chez 160 femmes fréquentant des cliniques de consultations obstétricales pour patientes exposées à des risques élevés au sein d'un établissement de soins tertiaires. Les prélèvements ont été répartis en deux aliquots : un aliquot a été testé au moyen de deux bandelettes réactives urinaires différentes (une faisant l'objet d'une lecture visuelle et l'autre faisant l'objet d'une lecture automatisée). Un deuxième aliquot utilisant la même urine a été analysé pour ce qui est des taux urinaires de protéines et de créatinine. Le rendement des résultats de la lecture visuelle et de la lecture automatisée (protéinurie ≥ 1+) a été comparé pour ce qui est de la détection d'un PrCr ≥ 30 mg/mmol au moyen de prélèvements d'urine non diluée (taux urinaire de créatinine ≥ 3 mmol/l). Résultats : Les deux bandelettes réactives urinaires ont présenté une faible sensibilité (lecture visuelle : 56,0 % et lecture automatisée : 53,8 %). Les rapports de vraisemblance positifs ont été de 15,0 pour le dépistage visuel par bandelette réactive urinaire (IC à 95 %, 5,9 - 37,9) et de 24,6 pour le dépistage automatisé par bandelette réactive urinaire (IC à 95 %, 7,6 - 79,6). Les rapports de vraisemblance négatifs ont été de 0,46 pour le dépistage visuel par bandelette réactive urinaire (IC à 95 %, 0,29 - 0,71) et de 0,47 pour le dépistage automatisé par bandelette réactive urinaire (IC à 95 %, 0,31 - 0,72). Conclusion : Le dépistage automatisé par bandelette réactive urinaire ne s'est pas révélé supérieur au dépistage visuel pour ce qui est de la détection de la protéinurie chez des femmes enceintes dans un contexte de services principalement externes. La sensibilité pourrait dépendre des bandelettes réactives et/ou de l'analyseur utilisés.

Glacial cycles as an allopatric speciation pump in north-eastern American freshwater fishes.

Allopatric speciation may be the principal mechanism generating new species. Yet, it remains difficult to judge the generality of this process because few studies have provided evidence that geographic isolation has triggered the development of reproductive isolation over multiple species of a regional fauna. Here, we first combine results from new empirical data sets (7 taxa) and published literature (9 taxa) to show that the eastern Great Lakes drainage represents a multispecies suture zone for glacial lineages of freshwater fishes with variable levels of genetic divergence. Second, we performed amplified fragment length polymorphism analyses among four pairs of lineages. Results indicate that lineages with relatively deep levels of mtDNA 5' COI (barcode) sequence divergence (>2%) developed strong reproductive barriers, while lineages with lower levels of divergence show weaker reproductive isolation when found in sympatry. This suggests that a threshold of 2% sequence divergence at mtDNA could be used as a first step to flag cryptic species in North American freshwater fishes. By describing different levels of divergence and reproductive isolation in different co-occurring fishes, we offer strong evidence that allopatric speciation has contributed significantly to the diversification of north-eastern American freshwater fishes and confirm that Pleistocene glacial cycles can be viewed as a 'speciation pump' that played a predominant role in generating biodiversity.

Unexpected random urinary protein:creatinine ratio results-limitations of the pyrocatechol violet-dye method.

BACKGROUND: For clinicians, it is important to rely on accurate laboratory results for patient care and optimal use of health care resources. We sought to explore our observations that urine protein:creatinine ratios (PrCr) ≥30 mg/mmol are seen not infrequently associated with normal pregnancy outcome. METHODS: Urine samples were collected prospectively from 160 pregnant women attending high-risk maternity clinics at a tertiary care facility. Urinary protein was measured using a pyrocatechol violet assay and urinary creatinine by an enzymatic method on Vitros analysers. Maternal/perinatal outcomes were abstracted from hospital records. RESULTS: 91/233 (39.1%) samples had a PrCr ≥30 mg/mmol, especially when urinary creatinine concentration was <3 mM (94.1%) vs. ≥3 mM (16.4%) (p < 0.001). When using the last sample before delivery, 47/160 (29.4%) had a PrCr ≥30 mg/mmol in diluted urine vs. only 17/160 (15.4%) in more concentrated urine (p < 0.001); PrCr positive results were also more frequent among the 32 (20.0%) women with known normal pregnancy outcome (90.9% vs. 0) (p < 0.001). Using the same analyser, 0.12 g/L urinary protein was 'detected' in deionised water. Re-analysis of data from two cohorts revealed substantially less inflation of PrCr in dilute urine using a pyrogallol red assay. CONCLUSIONS: Random urinary PrCr was overestimated in dilute urine when tested using a common pyrocatechol violet dye-based method. This effect was reduced in cohorts when pyrogallol red assays were used. False positive results can impact on diagnosis and patient care. This highlights the need for both clinical and laboratory quality improvement projects and standardization of laboratory protein measurement.

Maternal and neonatal complications during delivery according to passive versus active second stage in woman with medical conditions (ComPActSS).

Background: The incidence of serious complications during vaginal delivery with a passive second stage in women with medical conditions is unknown. Methods: Our retrospective cohort study with matched groups (pairing 1 passive with 2 active second stage) included women who had a medical delivery plan from the high risk obstetric team at our center. The primary outcome was a composite of major maternal and neonatal complications. Results: The primary outcome occurred in 50% (12/24) of women in the passive group versus 35.4% (17/48) (p = 0.24) in the active group. In the passive group, we observed a longer passive second stage of labor (28 vs. 8 min, p < 0.001), a tendency towards more assisted vaginal births (29.2% vs. 12.5%, p = 0.08), and more traumatic deliveries (16.7% vs. 0%, p = 0.012). Conclusion: The higher proportion of complications in women who had a passive second stage should encourage physicians to make this recommendation only in selected cases.