Acute lithiasis cholangitis is rare in pregnancy. More difficult than diagnosis is prognosis for both mother and fetus, conditioned by management, which is not well codified, and must be adapted to each case. We reported clinical and paraclinical features of acute cholangitis in pregnant women, as well as management modalities.

BJOG Commentary  Title: Fetal movement trials: where is the evidence in settings with high burden of stillbirths?Authors: Natasha Housseine1,2, [email protected], [email protected] Browne2, [email protected] Maaløe3 [email protected] Sequeira Dmello1,4 [email protected] Ali2,5, [email protected] Abeid1, [email protected] Meguid6, [email protected] J Rijken2,7,8, [email protected] Kidanto1, [email protected] Affiliations 1.      Aga Khan University, Medical College East Africa, Dar es Salaam campus2.      Julius Global Health, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, The Netherlands3.      Global Health Section, Department of Public Health, University of Copenhagen, Denmark4.      Comprehensive Community Based Rehabilitation in Tanzania, Dar es salaam, Tanzania5.      Research Department, Ernest Cook Ultrasound Research and Education Institute (ECUREI), P.O. Box 7161, Kampala, Uganda6.      Child Health Unit, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa7.      Vrouw en Baby department, University Medical Centre Utrecht, Utrecht University, The Netherlands8.      Obstetric department, Amsterdam University Medical Center, Amsterdam, The Netherlands Corresponding author:Natasha HousseineThe Aga Khan University Medical CollegeUfukoni Road, P. O. Box 38129, Dar es salaam, Tanzania Telephone: +255 745 338 950  Fetal movement (FM) is a sign of fetal life and wellbeing that is felt by the pregnant woman, and reduced FM is known to precede stillbirths (1,2). Therefore, healthcare providers may advise women to monitor and report if their babies’ movements are fewer than usual. In high-income countries (HIC), there has been a renewed interest in FM with a recent wave of large-scale randomised controlled clinical trials investigating its potential to reduce stillbirths. The My Baby’s Movement trial in Australia/New Zealand, and the Mindfetalness trial in Sweden investigated the effects of intervention aimed at increasing women’s awareness of FM (3,4). The British AFFIRM trial investigated the effects of an FM awareness package coupled with a standardised management protocol (5). The ongoing CEPRA study in the Netherlands, UK and Australia and aims to evaluate Cerebro Placental Ratio as an indicator for delivery in women with reduced FM (6). None of the completed trials, however, found significant reductions in stillbirths. Moreover, they showed conflicting results on some potential harmful consequences, such as increased rates of obstetric interventions. In this commentary, we reflect on these trials through a global lens, and we urgently call for more trials – but this time in settings suffering the majority (98%) of the world’s two million annual stillbirths. Importantly, the global applicability of these HIC trials is questionable. They were conducted in settings where women are aware of the importance of reduced FM and are empowered to access highest standards of care. The contextual realities of pregnancy care are vastly different in low- and middle-income countries (LMICs) where antenatal care and health education are substandard. Women lack health information to self-monitor and report reduced FM. Furthermore, antenatal clinics are often overcrowded and understaffed, with lack of supplies, clinical guidelines, and adequate training of health workers. Recent estimates show stillbirth rates as high as 22 per 1000 per total births in Sub-Saharan Africa, compared to less than 3 per 1000 in HICs (7). Given the downward trend of stillbirths reported in all the HIC trials, it is possible that the completed trials may be demonstrating a lack of evidence rather than a lack of effectiveness. We hypothesise that involving women in their care, through training on how to monitor their baby’s movement and when and how to respond coupled with strengthening healthcare workers’ respect and response to women’s concerns on reduced FM, is a low-cost intervention with potential to significantly reduce stillbirths in high-burden LMICs. Surprisingly, high-quality studies from LMICs that have assessed the effect of FM interventions on perinatal deaths are lacking (2). Of note, the authors of the above-mentioned trials did not consider the well-known major differences in clinical context globally as a limitation while discussing the generalisability of their findings. In fact, the latest My Baby’s Movement trial was not even published open access, limiting access to less privileged clinicians, researchers and policymakers (4). This lack of a global perspective on the international health crisis of preventable stillbirths is an epistemic injustice and a missed opportunity (8). We are concerned that the results of the above trials could prematurely prompt policies discouraging the use of FM awareness among pregnant women (9). It is thus crucial that the lack of generic applicability of these trials’ findings are stressed, and that their high-resource contexts are considered when developing global clinical guidelines and future research priorities. Notably, it has been seen too often how the unbalanced evidence production from HICs has had unintended harmful influences on clinical practice in LMICs (10). For instance, it appears that the breech trials from HICs have led to policy change also in LMICs with increased use of caesarean section in case of breech presentation. However, the risk ratios of vaginal breech births versus caesarean sections differ dramatically between high-resource and low-resource settings with lower surgical safety in LMICs (11,12).The prevailing constraints in LMICs should stimulate innovation and creativity to design low-cost solutions that strengthen three areas 1) FM awareness and monitoring; 2) diagnosis to identify babies truly at risk, and 3) care provision protocols of pregnant women with reduced FM to improve perinatal outcomes. While such strategies or their evidence base are often lacking in LMICs, there is some evidence about possible low-cost diagnostic approaches to assess fetal risk following reduced FM: for example, measuring maternal blood pressure, fetal heart rate, and fundal height (13), or antenatal (hand-held) ultrasound to detect and monitor high-risk pregnancies. Measuring fetal blood flow in Doppler ultrasound studies has also been useful particularly in detecting growth restriction (6,14).  Involving women and health workers in studies will ensure consideration of health-system constraints and allow these to be embedded in the design, implementation, and evaluation of any new intervention. If proven effective, this will increase the chance of seamless integration of the intervention into existing care, positive perceptions by providers and pregnant women- and not increase the burden on already overwhelmed healthcare workers.  Unfortunately, maternal perception of FM is still too often the only signal of complications in the absence of regular high-quality antenatal checks (15)– and there are possibly many babies’ lives lost by ignoring this danger sign. Given the burden of need and the context-specific realities that determine interventions’ effectiveness, we hope these recent waves of FM trials will continue into LMICs to investigate if and how FM awareness coupled with context-tailored management protocol can reduce stillbirths.    Contribution to AuthorshipNH conceived and wrote the first draft. JB, NM, BSD and MJR contributed to subsequent drafting of the manuscript. All authors revised the commentary for important intellectual content and approved the final version to be published and agree to be accountable for all aspects of the work. Details of ethics approvalNo ethics approval applicable for this commentary FundingThere was no financial support for this commentary Disclosure of interests  Reference1.        Bekiou A, Gourounti K. Reduced Fetal Movements and Perinatal Mortality. Mater Sociomed. 2020;32(3). 2.        Hayes DJL, Smyth R, Heazell AEP. Investigating the significance and current state of knowledge and practice of absent or reduced fetal movements in low and lower middle-income countries : a scoping review. 2019;3:1–12. 3.        Akselsson A, Lindgren H, Georgsson S, Pettersson K, Steineck G, Skokic V, et al. Mindfetalness to increase women’s awareness of fetal movements and pregnancy outcomes: a cluster-randomised controlled trial including 39 865 women. BJOG An Int J Obstet Gynaecol. 2020 Jun 1;127(7):829–37. 4.        Flenady V, Gardener G, Ellwood D, Coory M, Weller M, Warrilow KA, et al. My Baby’s Movements: a stepped-wedge cluster-randomised controlled trial of a fetal movement awareness intervention to reduce stillbirths. BJOG An Int J Obstet Gynaecol. 2022 Jan 1;129(1):29–41. 5.        Norman JE, Heazell AEP, Rodriguez A, Weir CJ, Stock SJE, Calderwood CJ, et al. Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM): a stepped wedge, cluster-randomised trial. www.thelancet.com. 2018;392. 6.        Damhuis SE, Ganzevoort W, Duijnhoven RG, Groen H, Kumar S, Heazell AEP, et al. The CErebro Placental RAtio as indicator for delivery following perception of reduced fetal movements, protocol for an international cluster randomised clinical trial; the CEPRA study. BMC Pregnancy Childbirth. 2021 Dec 1;21(1). 7.        Hug L, You D, Blencowe H, Mishra A, Wang Z, Fix MJ, et al. Global, regional, and national estimates and trends in stillbirths from 2000 to 2019: a systematic assessment. Lancet. 2021 Aug 28;398(10302):772–85. 8.        Bhakuni H, Abimbola S. Epistemic injustice in academic global health. Lancet Glob Heal. 2021;9:e1465–70. 9.        Walker KF, Thornton JG. Encouraging awareness of fetal movements is harmful. Lancet. 2018 Nov 3;392(10158):1601–2. 10.      Maaløe N, Ørtved AMR, Sørensen JB, Sequeira Dmello B, van den Akker T, Kujabi ML, et al. The injustice of unfit clinical practice guidelines in low-resource realities. Lancet Glob Heal. 2021;9(6):e875–9. 11.      van Roosmalen J, Meguid T. The dilemma of vaginal breech delivery worldwide. Lancet. 2014;338(9932): 12.      Sobhy S, Arroyo-Manzano D, Murugesu N, Karthikeyan G, Kumar V, Kaur I, et al. Maternal and perinatal mortality and complications associated with caesarean section in low-income and middle-income countries: a systematic review and meta-analysis. Lancet. 2019 May 11;393(10184):1973–82. 13.      Housseine N, Rijken MJ, Weller K, Nassor NH, Gbenga K, Dodd C, et al. Development of a clinical prediction model for perinatal deaths in low resource settings. eClinicalMedicine. 2022 Feb;44:101288. 14.      Ali S, Kawooya MG, Byamugisha J, Kakibogo IM, Biira EA, Kagimu AN, et al. Middle cerebral arterial flow redistribution is an indicator for intrauterine fetal compromise in late pregnancy in low-resource settings: a prospective cohort study. BJOG An Int J Obstet Gynaecol. 2022 Feb 4; 15.      World Health Organization. WHO recommendations on antenatal care for a positive pregnancy experience [Internet]. 2016 [cited 2020 Jul 30]. Available from: https://www.who.int/reproductivehealth/publications/maternal_perinatal_health/anc-positive-pregnancy-experience/en/ ‘This article has a Video Abstract presented by Natasha Housseine.’

People with cystic fibrosis (CF) have an amazing outlook with the treatment availability of highly effective modulators. Unfortunately, not all PwCF are eligible for modulators leading to continued pulmonary exacerbations and advanced lung disease. Additionally, optimizing diagnosis and evaluation for CF in the newborn period continues to be an area of focus for research. This review article will work to cover articles published in 2021 with high clinical relevance related to the above topics, however due to the extensive body of research published, this review will not be comprehensive.

COVID-19 related MIS-C (Multisystem inflammatory syndrome in children) can present with cardiovascular complications like shock, arrhythmias, pericardial effusion, and coronary artery dilatation. The majority of MIS-C associated coronary artery abnormalities are dilation or small aneurysms which are transient and resolve in a few weeks[[1, 2]](#ref-0001). We present here a case of a 3-month-old child who was noted to have giant aneurysms of her coronary arteries (LAD and RCA) twenty-six days after testing positive for COVID-19. She was treated with IVIG, infliximab, and glucocorticoids along with aspirin, clopidogrel and enoxaparin. She did not show any signs of coronary ischemia or cardiac dysfunction but continued to have persistent giant coronary artery aneurysms involving the LAD (z-score ~35) and RCA (z-score ~30) [Fig. 1]. This study emphasizes the importance of early detection and aggressive management of MIS-C to prevent potentially life-threatening consequences.

The maximum tangential stress (MTS) criterion is one of the most widely used criteria for predicting the direction of crack extension. The suitability of this criterion is examined under different loading conditions using extended finite element method (XFEM). Experimental and numerical results reported in the literature are considered to evaluate the validity and accuracy of the criterion. The results demonstrate that the MTS criterion evaluated by stress intensity factors (SIF) can accurately predict the direction of crack propagation in specimens under direct tensile loading. This criterion overestimates the angle of crack initiation in the specimen under indirect tensile loading, but underestimates the angle in the specimen subjected to three-point bending. It is concluded that the MTS criterion based on SIF could not accurately predict the direction of the crack initiation, which could, however, be determined properly based on the stress distribution around the crack tip obtained by XFEM numerical models.

Using indocyanine green(ICG), a standard reagent used in liver function tests, bile leaks from exfoliated liver sections can be detected with higher sensitivity than observation with the naked eye. This presentation will introduce the technique of using ICG to detect bile leaks that cannot be detected by the naked eye.

The inappropriate use of insecticides may lead to disastrous pest outbreaks. Aiming at avoiding the outbreak of pests by optimizing the control strategies, we propose a novel mathematical model base on the idea of pulse in this study, namely a discrete-time model of pest-natural enemies, which considers the implementation of spraying insecticides within the time interval between two generations of pests. We first investigates the existence and stability of fixed points, and then using the central manifold theory, we proved that the system can exist period-doubling bifurcation. The main theoretical results are verified by numerical simulations. The experiments show that if the insecticidal time is within a certain range, the lower insecticidal rate stimulates the growth of pests and natural enemies, while the larger insecticidal rate can inhibit the growth of pests and natural enemies. In addition, the effects of pest growth rate, timing of pesticide spraying, and pesticide intensity on the system are comprehensively discussed. The main research provides good reference significance to choose an appropriate time to prevent the pest outbreaks.

There is currently a lack of evidence surrounding changes in the health of riparian zones under different land-use patterns within mega-reservoirs and around dams. Scientific evidence for the quantitative effects of stress indicators is vague and varies significantly among reservoirs and dams worldwide. In this study, we used a field-based approach to evaluate riparian health changes—influenced by pressure indicators—across 274 transects from three land-use areas (rural, rural–urban transitional, and urban) in the Three Gorges Dam Reservoir (TGDR) in China during 2019. Multivariate statistical techniques were applied to test for riparian zone changes under these variant land-use patterns. Our results showed that 13 pressure indicators significantly influenced 27 health indicators (including parameters for habitat, plant cover, regeneration, erosion, and exotics) of the riparian zones from the three land-use areas differently. Our results also showed that parameters for plant cover, erosion, and exotics were major contributors within the selected riparian health indicators, whereas land-use designs, farming systems, and pollutant activity variables were the pressure indicators with the strongest impact. Pearson correlation (with r ranging from -0.731 to 0.989) showed that urban transects exhibited the strongest comparative interaction, whereas rural–urban transitional transects formed the weakest association. Furthermore, the agglomerative hierarchical cluster analysis revealed similarities between rural and rural–urban transitional sites while confirming substantial dissimilarity in urban locations. These comprehensive and relevant results provide essential information for reservoir administrators to implement functional changes suited to TGDR land-use scenarios.

Rheumatic manifestations can reveal hypothyroidism, such as arthritis and non-specific musculoskeletal symptoms. We report herein the case of an acute polyarthritis revealing Hashimoto's thyroiditis. Hormone replacement therapy leads to the resolution of arthritis related to Hashimoto's thyroiditis, suggesting the role of thyroid hormone in the pathogenesis of arthritis.

Quinoa (Chenopodium quinoa), a herbaceous annual, has been widely cultivated in recent years because of its high nutritional value and strong tolerance to abiotic stresses. The study was conducted at two planting densities (LD, 10 plants/m2; HD, 65 plants/m2) on ameliorated coastal mudflats in Jiangsu Province, China (118° 46′ E, 32° 03′ N). The results showed soil salinity and organic matter were higher in the HD than LD treatment, and salinity of the rhizosphere soil was higher than that of the non-rhizosphere soil. Quinoa grown in HD was taller, with thicker stalks and lower yields per plant, but higher yield per unit area. Amplicon sequencing showed that Proteobacteria, Bacteroidota and Acidobacteria were the dominant bacterial phyla. Regarding the rhizosphere soil, the Shannon index was higher in the HD than LD, and Proteobacteria and Bacteroidota were more abundant in the HD treatment. Fifty-one differential metabolites were identified by metabolomic assays, belonging to 14 annotated metabolic pathways. S-adenosylmethionine was the most abundant and up-regulated metabolite (fold change >1.67), and was more abundant in the roots from the LD than HD treatment. Docosahexaenoic acid was more abundant in the HD than LD treatment, and was down-regulated metabolite. In conclusion, planting density was an important factor affecting quinoa yield; compared with unplanted soil, planting quinoa at low density increased the content of the important metabolite S-adenosylmethionine in the root system of quinoa, and high density cultivation of quinoa increased soil salinity and microbial abundance and diversity.

The fracture behavior of ultra-high temperature ceramic matrix composites at high temperature has received increasing attention. However, few studies consider the effect of particle/crack interaction on the high temperature fracture strength. In this work, based on the energy storage capacity, energy balance method and fracture theory, the effect of particle/crack interaction is introduced into a temperature-dependent fracture strength model of monolithic ultra-high temperature ceramic matrix composites, which also considers effects of flaw size, grain size and residual thermal stress. Furthermore, by considering the influence of the laminated structure, a theoretical characterization model of the temperature-dependent fracture strength of laminated ceramic matrix composites is developed. The effect of particle/crack interaction is also included in this model. It should be noted that the predictions of the models agree well with the experimental data of both monolithic and laminated materials without using any fitting parameters. The effect of particle/crack interaction is found to have a significant weakening effect on the strength of materials at different temperatures. The theoretical models only need some simple basic material parameters to predict the fracture strength and mechanisms of ceramic matrix composites at high temperature, which have important practical significance for engineering applications.

In this special issue of the British Journal of Clinical Pharmacology, we highlight innovative methodologies in pediatric drug development.

A document by Bilawal Nadeem. Click on the document to view its contents.

Mitochondria continuously undergo morphologically dynamic processes of fusion and fission to maintain their size, shape, amount, and function; yet the precise molecular mechanisms by which mitochondrial dynamics is regulated remain to be fully elucidated. Here, we report a previous unappreciated but critical role of eukaryotic elongation factor 2 (eEF2) in regulating mitochondrial fission. eEF2, a G-protein superfamily member encoded by EEF2 gene in human, has long been appreciated as a promoter of the GTP-dependent translocation of the ribosome during protein synthesis. We found unexpectedly in several types of cells that eEF2 was not only present in the cytosol but also in the mitochondria. Furthermore, we showed that mitochondrial length was significantly increased when the cells were subjected to silencing of eEF2 expression, suggesting a promotive role for eEF2 in the mitochondrial fission. Inversely, overexpression of eEF2 decreased mitochondrial length, suggesting an increase of mitochondrial fission. Inhibition of mitochondrial fission caused by eEF2 depletion was accompanied by alterations of cellular metabolism, as evidenced by a reduction of oxygen consumption and an increase of oxidative stress in the mitochondria. We further demonstrated that eEF2 and Drp1, a key driver of mitochondrial fission, co-localized at the mitochondria, as evidenced by microscopic observation, co-immunoprecipitation, and GST pulldown assay. Deletion of the GTP binding motif of eEF2 decreased its association with Drp1 and abrogated its effect on mitochondria fission. Moreover, we showed that wild-type eEF2 stimulated GTPase activity of Drp1, whereas deletion of the GTP binding site of eEF2 diminished its stimulatory effect on GTPase activity. This work not only reveals a previously unrecognized function of eEF2 (i.e., promoting mitochondrial fission), but also uncovers the interaction of eEF2 with Drp1 as a novel regulatory mechanism of the mitochondrial dynamics. Therefore, eEF2 warrants further exploration for its potential as a therapeutic target for the mitochondria-related diseases.

Background. Current temporary transvenous pacemaker catheters lack sequential atrioventricular (AV) pacing in synchrony. Therefore, a catheter that could provide sequential AV pacing and maintain synchrony may be useful for patients in sinus rhythm who need temporary pacing.  Objective. The purpose of this study was to describe the first in human experience with a novel temporary AV sequential pacing catheter (TAVSP). Methods. We prospectively identified eligible patients undergoing elective cardiac catheterization in whom the TAVSP catheter was delivered and used for temporary AV sequential pacing. Safety endpoints and device performance data were obtained. Results. Ten subjects were screened and enrolled in the study. TAVSP was delivered in all ten subjects, and AV sequential synchronous pacing was successfully obtained. The pacing catheter achieved an excellent pacing threshold and impedance in all ten patients except for one. There were no adverse events during the pacing procedure. Conclusion. Temporary AV sequential pacing using TAVSP catheter is safe and feasible and may be an alternative to conventional temporary pacing catheters to maintain AV synchrony during temporary pacing.

TYPE OF ARTICLE: LETTER TO EDITOR

The potential for forecasting the dynamics of ecological systems is currently unclear, with contrasting opinions regarding its feasibility due to ecological complexity. To investigate forecast skill within and across system complexity, we monitored a microbial system exposed to either constant or fluctuating temperatures in a five months long laboratory experiment. We tested how forecasting of species abundances depends on number and strength of interactions and on model size (number of predictors). We also tested how greater system complexity (i.e. the fluctuating temperatures) impacted these relations. We found that the more a species interacted, the weaker these interactions were and the better its abundance was predicted. Forecast skill increased with model size. Greater system complexity decreased forecast skill for three out of eight species. These insights into how abundance prediction depends on the embedding of the species within the system and on overall system complexity could improve species forecasting and monitoring.

Secondary forest restoration can alter terrestrial ecosystem processes and potentially impact subsurface carbon dynamics. However, the effects of long-term forest restoration on the soil microbial metabolic activity remain unclear. So, the aim of this study was to explore the response of soil microbial metabolism to forest restoration. Among them, the soil basal respiration (BR), microbial quotient ( qMB), and metabolic quotient ( qCO 2) were studied. This study investigated a natural vegetation restoration sequence approximately ~160 years after farmland abandonment on the central Loess Plateau, China, corresponding to five vegetation restoration stages including farmland, grassland, shrubland, pioneer forests, and climax forests. The results showed that BR and qCO 2 were increased following forest restoration, whereas qMB showed the opposite trend. Forest restoration also increased the activities of β-1,4-glucosidase and β-D-cellobiosidase. Restoration age, litter traits such as nitrogen, cellulose and lignin decomposition rates, dissolved organic carbon contents, fungi and bacteria composition were also important indicators affecting microbial metabolic activities. Long-term forest restoration can change soil microbial community structure, reduce carbon mineralization efficiency, improve soil microbial carbon utilization efficiency, and promote soil organic carbon accumulation.