Mitral valve prolapse: arrhythmic risk during pregnancy and postpartum.

BACKGROUND AND AIMS: Arrhythmic mitral valve prolapse (AMVP) is linked to life-threatening ventricular arrhythmias (VAs), and young women are considered at high risk. Cases of AMVP in women with malignant VA during pregnancy have emerged, but the arrhythmic risk during pregnancy is unknown. The authors aimed to describe features of women with high-risk AMVP who developed malignant VA during the perinatal period and to assess if pregnancy and the postpartum period were associated with a higher risk of malignant VA. METHODS: This retrospective international multi-centre case series included high-risk women with AMVP who experienced malignant VA and at least one pregnancy. Malignant VA included ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock from an implantable cardioverter defibrillator. The authors compared the incidence of malignant VA in non-pregnant periods and perinatal period; the latter defined as occurring during pregnancy and within 6 months after delivery. RESULTS: The authors included 18 women with AMVP from 11 centres. During 7.5 (interquartile range 5.8-16.6) years of follow-up, 37 malignant VAs occurred, of which 18 were pregnancy related occurring in 13 (72%) unique patients. Pregnancy and 6 months after delivery showed increased incidence rate of malignant VA compared to the non-pregnancy period (univariate incidence rate ratio 2.66, 95% confidence interval 1.23-5.76). CONCLUSIONS: The perinatal period could impose increased risk of malignant VA in women with high-risk AMVP. The data may provide general guidance for pre-conception counselling and for nuanced shared decision-making between patients and clinicians.

Priorities, opportunities, and challenges for integrating microorganisms into Earth system models for climate change prediction.

Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.

Microbiology and Climate Change: a Transdisciplinary Imperative.

Climate change is a complex problem involving nonlinearities and feedback that operate across scales. No single discipline or way of thinking can effectively address the climate crisis. Teams of natural scientists, social scientists, engineers, economists, and policymakers must work together to understand, predict, and mitigate the rapidly accelerating impacts of climate change. Transdisciplinary approaches are urgently needed to address the role that microorganisms play in climate change. Here, we demonstrate with case studies how diverse teams and perspectives provide climate-change insight related to the range expansion of emerging fungal pathogens, technological solutions for harmful cyanobacterial blooms, and the prediction of disease-causing microorganisms and their vector populations using massive networks of monitoring stations. To serve as valuable members of a transdisciplinary climate research team, microbiologists must reach beyond the boundaries of their immediate areas of scientific expertise and engage in efforts to build open-minded teams aimed at scalable technologies and adoptable policies.

A comparison of node vaccination strategies to halt SIR epidemic spreading in real-world complex networks.

We compared seven node vaccination strategies in twelve real-world complex networks. The node vaccination strategies are modeled as node removal on networks. We performed node vaccination strategies both removing nodes according to the initial network structure, i.e., non-adaptive approach, and performing partial node rank recalculation after node removal, i.e., semi-adaptive approach. To quantify the efficacy of each vaccination strategy, we used three epidemic spread indicators: the size of the largest connected component, the total number of infected at the end of the epidemic, and the maximum number of simultaneously infected individuals. We show that the best vaccination strategies in the non-adaptive and semi-adaptive approaches are different and that the best strategy also depends on the number of available vaccines. Furthermore, a partial recalculation of the node centrality increases the efficacy of the vaccination strategies by up to 80%.

Analgesic Efficacy of Pfannenstiel Incision Infiltration with Ropivacaine 7.5 mg/mL for Caesarean Section.

Background. Pain after Caesarean delivery is partly related to Pfannenstiel incision, which can be infiltrated with local anaesthetic solutions. Methods. A double- blind randomized control trial was designed to assess the analgesic efficacy of 7.5 mg/mL ropivacaine solution compared to control group, in two groups of one hundred and forty four parturients for each group, who underwent Caesarean section under spinal anaesthesia: group R (ropivacaine group) and group C (control group). All parturients also received spinal sufentanil (2.5 mug). Results. Ropivacaine infiltration in the Pfannenstiel incision for Caesarean delivery before wound closure leads to a reduction of 30% in the overall consumption of analgesics (348 550 mg for group R versus 504 426 mg for group C with P < .05), especially opioids in the first 24 hours, but also significantly increases the time interval until the first request for an analgesic (4 h 20 min +/- 2 h 26 for group R versus 2 h 42 +/- 1 h 30 for group C). The P values for the two groups were: P < .0001 for paracetamol, P < .0001 for ketoprofen and P for nalbuphine which was the most significant. There is no significant difference in the threshold of VAS in the two series. Conclusion. This technique can contribute towards a programme of early rehabilitation in sectioned mothers, with earlier discharge from the post-labour suite.

Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture.

Stem cells that naturally reside in adult tissues, such as muscle stem cells (MuSCs), exhibit robust regenerative capacity in vivo that is rapidly lost in culture. Using a bioengineered substrate to recapitulate key biophysical and biochemical niche features in conjunction with a highly automated single-cell tracking algorithm, we show that substrate elasticity is a potent regulator of MuSC fate in culture. Unlike MuSCs on rigid plastic dishes (approximately 10(6) kilopascals), MuSCs cultured on soft hydrogel substrates that mimic the elasticity of muscle (12 kilopascals) self-renew in vitro and contribute extensively to muscle regeneration when subsequently transplanted into mice and assayed histologically and quantitatively by noninvasive bioluminescence imaging. Our studies provide novel evidence that by recapitulating physiological tissue rigidity, propagation of adult muscle stem cells is possible, enabling future cell-based therapies for muscle-wasting diseases.

Effect of chronic psychosocial stress-induced by subordinate colony (CSC) housing on brain neuronal activity patterns in mice.

Chronic subordinate colony (CSC) housing has been recently validated as a murine model of chronic psychosocial stress which induces alterations of stress-related parameters including decreased body-weight gain and an increased level of anxiety in comparison with single housed control (SHC) mice. By using immunohistochemical immediate early gene (IEG) mapping we investigated whether CSC housing causes alterations in neuronal activation patterns in limbic areas including the amygdala, hippocampus, septum and the periaqueductal gray (PAG) and hypothalamic paraventricular nucleus (PVN). While CSC housing increased basal Zif-268 expression in the nucleus accumbens shell compared to SHC, IEG responses to subsequent open arm (OA) exposure were attenuated in the ventral and intermediate sub-regions of the lateral septum, parvocellular PVN and the dorsal CA3 region of the hippocampus of CSC compared with SHC mice. In contrast, a potentiated c-Fos response in CSC mice was observed in the dorsomedial PAG after OA exposure. Confirming previous findings obtained on the elevated plus-maze, an enhanced anxiety-related behavior in CSC compared with SHC mice was also observed during OA exposure. In order to investigate the appropriate control conditions for CSC housing, group housed control (GHC) mice were additionally included in the behavioral testing. Interestingly, GHC as well as CSC mice showed significantly less risk assessment/exploratory behavior during OA exposure compared with SHC mice indicating that group housing itself is stressful for mice and not an adequate control for the CSC paradigm. Overall, CSC housing is an ethologically relevant chronic psychosocial stressor which results in an elevated sensitivity to a subsequent novel, aversive challenge. However, the CSC-induced increase in anxiety-related behavior was accompanied by differences in neuronal activation, compared with SHC, in defined sub-regions of brain areas known to be involved in the processing of emotionality and stress responses.

Role of voltage-gated L-type Ca2+ channel isoforms for brain function.

Voltage-gated LTCCs (L-type Ca2+ channels) are established drug targets for the treatment of cardiovascular diseases. LTCCs are also expressed outside the cardiovascular system. In the brain, LTCCs control synaptic plasticity in neurons, and DHP (dihydropyridine) LTCC blockers such as nifedipine modulate brain function (such as fear memory extinction and depression-like behaviour). Voltage-sensitive Ca2+ channels Cav1 .2 and Cav1.3 are the predominant brain LTCCs. As DHPs and other classes of organic LTCC blockers inhibit both isoforms, their pharmacological distinction is impossible and their individual contributions to defined brain functions remain largely unknown. Here, we summarize our recent experiments with two genetically modified mouse strains, which we generated to explore the individual biophysical features of Cav1.2 and Cav1.3 LTCCs and to determine their relative contributions to various physiological peripheral and neuronal functions. The results described here also allow predictions about the pharmacotherapeutic potential of isoform-selective LTCC modulators.

Methylation of the p16(INK4a) promoter region in telomerase immortalized human keratinocytes co-cultured with feeder cells.

Human keratinocytes grown in co-culture with fibroblast feeder cells have an extended in vitro lifespan and delayed accumulation of the tumor suppressor protein p16(INK4a) when compared to the same cells grown on tissue culture plastic alone. Previous studies have indicated that human keratinocytes can be immortalized by telomerase activity alone when grown in co-culture with feeder cells, suggesting that loss of the p16(INK4a)/Rb pathway is not required for immortalization. Using two independent human keratinocyte cell strains, we found that exogenous telomerase expression and co-culture with feeder cells results in efficient extension of lifespan without an apparent crisis. However, when these cells were transferred from the co-culture environment to plastic alone they experienced only a brief period of slowed growth before continuing to proliferate indefinitely. Examination of immortal cell lines demonstrated p16(INK4a) promoter methylation had occurred in both the absence and presence of feeder cells. Reintroduction of p16(INK4a) into immortal cell lines resulted in rapid growth arrest. Our results suggest that p16(INK4a)/Rb-induced telomere-independent senescence, although delayed in the presence of feeders, still provides a proliferation barrier to human keratinocytes in this culture system and that extended culture of telomerase-transduced keratinocytes on feeders can lead to the methylation of p16(INK4a).

MR imaging in shoulder trauma. Value of STIR images.

PURPOSE: To determine the adequacy of MR standard protocols by analyzing conventional T1- and T2-weighted SE sequences, and to evaluate the usefulness of additional fat-suppressed (STIR) images in shoulder trauma. MATERIAL AND METHODS: Paracoronal T1-weighted, T2-weighted, SE, and STIR images were obtained on a 0.5 T superconductive system in 25 patients with shoulder trauma. In a separate evaluation of T1/T2 images and a combined evaluation of T1/T2 SE- and STIR images, we compared the number of patients with evidence of Hill-Sachs lesions, bone bruises, and/or rotator-cuff lesions. RESULTS: Compared to the combined evaluation of T1/T2 and STIR images, the separate evaluation of T1/T2 SE images revealed identical results for rotator-cuff lesions and Hill-Sachs lesions, but different results for the bone bruises in the area of the major tubercle. CONCLUSION: Occult fractures of the major tubercle, indicated by areas of bone bruising, might be missed with MR using conventional SE images. We recommend the use of additional paracoronal fat-suppressed sequences in patients with clinically suspected lesions and equivocal findings on plain radiographs and on standard SE sequences.

[Anesthesia for heart catheterization in children. Comparison of 3 techniques]. / Anesthésie pour cathétérisme cardiaque chez l'enfant: comparaison de trois techniques.

A study was carried out to compare the haemodynamic and respiratory effects, as well as the quality of recovery, of anaesthesia with ketamine, sodium gamma-hydroxybutyrate (GOH) and etomidate in children undergoing cardiac catheterization. Thirty children, mean age 48 +/- 35 months, ranked ASA 2 or 3 on account of congenital heart disease, were assigned to one of three groups (n = 10). They were given: in group E1, a 0.3 mg.kg-1 bolus of etomidate, followed by 0.1 mg.kg-1.min-1 for 10 minutes, and 0.026 mg.kg-1.min-1 thereafter; in group G2, a 50 mg.kg-1 bolus of GOH, and in group K3, a 4 mg.kg-1 bolus of ketamine followed by a continuous infusion of 0.083 mg.kg-1.min-1. The patients breathed spontaneously. Monitoring included heart rate, systolic, diastolic and mean blood pressure, pulse oximetry, and capnography. Femoral venous or arterial catheterization was performed after local anaesthesia (with no more than 2 mg.kg-1 of lidocaine). Measurements were performed before induction, and then 1, 10, 30 and 60 minutes afterwards. The quality of anaesthesia was assessed according to Steward's scale. The investigation lasted between 50 and 100 min in all three groups. There were no significant differences in haemodynamic and respiratory parameters during the investigation between the groups. Recovery was shorter and of better quality in group E1. On the opposite, 30 minutes after the end of the catheterization, all the patients in group K3 were stuporous, with 5 of them displaying involuntary movements. The patients of the other two groups reacted correctly to stimuli, but those in group G2 went back to sleep very rapidly. There were no complications.(ABSTRACT TRUNCATED AT 250 WORDS)