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Abstract This study evaluated the impact of differential sowing windows and improved weed management strategies on weed dynamics, productivity, and economic viability of direct drum seeded rice (Oryza sativa L.) in the temperate agro-ecosystem of Kashmir. A two-year field experiment was conducted utilizing a split-plot design with two sowing dates (May 10 and June 3) as main plots and six weed management practices as sub-plots. The earlier sowing date (May 10) resulted in significantly enhanced leaf area index, crop growth rate, relative growth rate, net assimilation rate, and grain and straw yields compared to the later sowing (June 3). Among weed management treatments, four mechanized conoweedings (equivalent to weed-free conditions) and sequential application of bensulfuron methyl + pretilachlor (60 and 600 g a.i. ha−1) as pre-emergence followed by 2,4-D (0.75 kg a.i. ha−1) as post-emergence demonstrated superior efficacy in weed suppression and augmentation of crop growth parameters and yield attributes. These treatments also exhibited the lowest weed index and highest benefit–cost ratio. The May 10 sowing, coupled with efficacious weed control measures, significantly reduced weed density and biomass while concomitantly improving nutrient uptake and economic returns. The results indicate that adopting a May 10 sowing date for direct seeded rice, in conjunction with either four conoweedings or the aforementioned sequential herbicide application, can optimize agronomic productivity and economic profitability under the temperate conditions of Kashmir. The study aided in choosing the best sowing window and efficient weed management strategy for attaining higher productivity and profitability of direct seeded rice in temperate conditions.

Background/Aim: Endometrial cancer is one of the most prevalent gynaecologic cancers in advanced nations and act as the largest proportion of tumours occurring in the uterine corpus. The aim of the study was to identify potential diagnostic biomarkers for endometrial cancer among the evaluated hormones and tumour markers to enhance early detection and improve patient outcomes. Methods: A comparison was made between two groups of women: 30 individuals who were healthy and 30 individuals who had endometrial cancer. The participants in both groups were carefully selected to ensure that they were similar in terms of age and body mass index (BMI). Luteinising hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), cancer antigen 125 (CA-125) and carcinoembryonic antigen (CEA) were analysed. Results: As compared to healthy individuals, females diagnosed with endometrial tumour and cancer exhibited notably elevated levels of LH, FSH, E2, CA-125 and CEA. Conversely, they demonstrated significantly reduced levels of prolactin in their serum. Conclusions: Endometrial cancer patients had significantly raised concentrations of LH, E2, FSH, PRL, CEA and CA-125 in their serum, indicating hormonal dysregulation in the development of endometrial cancer. It is not advisable to rely solely on LH, E2, FSH, PRL, CA-125 or CEA as screening markers for endometrial cancer. Instead, they should be considered as part of a comprehensive screening panel that needs to be developed in the future.

Ayat A Awwad,1 Osama MM Abd Elhay,2 Moustafa M Rabie,3 Eman A Awad,4 Fatma M Kotb,4 Hend M Maghraby,4 Rmadan H Eldamarawy,4 Yahia MA Dawood,1 Mostafa IEI Balat,1 Ahmed IM Hasan,5 Ahmed H Elsheshiny,6 Said SMM El Sayed,2 Albayoumi AB Fouda,2 Ahmad MF Alkot2 1Otorhinolaryngology department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 2Medical Physiology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 3Public Health and Community Medicine Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 4Internal medicine department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 5Pediatric Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 6Neurology department, Faculty of Medicine, Al-Azhar University, Cairo, EgyptCorrespondence: Ayat A Awwad, Otorhinolaryngology department, Faculty of Medicine, Al-Azhar University, Al Zhraa University Hhospital, Alabasia, Cairo, 11517, Egypt, Email ayatnasr7419@yahoo.com; dr.ayat@azhar.edu.eg Osama MM Abd Elhay, Medical Physiology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt, Email osama.m.m.abdelhay@gmail.com; osamaabdelhay@domazhermedicine.edu.egBackground: COVID-19 (SARS-CoV-2/2019-nCoV) is now a major public health threat to the world. Olfactory dysfunctions (ODs) are considered potential indicating symptoms and early case identification triaging for coronavirus disease 2019 (COVID-19). The most common reported comorbidities are diabetes mellitus, chronic lung disease, and cardiovascular disease. The objective of this study was to evaluate prevalence of different types of smell disorders in patients with laboratory-confirmed COVID-19 infection and impact of involved systemic diseases.Methodology: A cross-sectional retrospective study has been done for patients with laboratory-confirmed COVID-19 infection (mild-to-moderate). The data collected from patient’s files and developed online electronic questionnaire (WhatsApp) based on the patients most common and recurrent reported data including: a) symptoms of olfactory dysfunction and associated covid19 symptoms fever and headache, cough, sore throat, pneumonia, nausea, vomiting and diarrhea, arthralgia and myalgia and taste dysfunction. b) Associated systemic diseases including: diabetes, hypertension, asthma, chronic renal disease, chorionic liver disease and hypothyroidism.Results: Of 308 patients confirmed with Covid-19 infection, (72.4%) developed OD distributed as follows; complete anosmia (57.8%), troposmia (8.4%), hyposmia (2.9%), partial anosmia (2.6%) and euosmia (0.6%). Significantly increased prevalence of diabetes, hypertension asthma in the group with olfactory dysfunction (p < 0.001), chronic liver disease (p = 0.005), and hypothyroidism (p = 0.03).Conclusion: The development of ODs after Covid-19 infection was associated with mild disease form and lower hospitalization. In addition, it showed significant relationship with preexisting systemic diseases. Anosmia is the common modality of ODs.Keywords: COVID-19, anosmia, olfactory dysfunction

The main purpose of this study is to simulate the long-term economic effects of government size on the economy and its expenditures combination based on Iran's budget structure over the next 20 years using the dynamic system of scenarios. In the first scenario, the increase in government size and the combination of government spending in the economy show that with the increase in government size, although the private sector investment trend is increasing in the short run, its level shifts and decreases from the previous path, and in the long run the private sector investment has declined; Furthermore, since government spends most of its revenue on running costs, production does not grow much in the long run as government size increases. In the second scenario, with the increase of the government's construction share of the total budget of the country, its short-term and long-term effects are systematically estimated. The results show that as the government's development share of the total budget increases, although private sector investment will increase more rapidly in the short term, in the long run the amount of private sector investment affected by other economic factors are declining, although GDP and national income are also increasing in the long run. Therefore, in order to increase production in the economy of Iran, economic development policymakers must effectively and efficiently increase public participation in the economy and reduce government size, by channeling the country's revenues and revenue sources in the development of infrastructure, technology, and production in the short term.

Abstract Background Over the past two decades, there has been a steady rise in the rate of Cesarean section delivery globally. As a result, short-term and long-term maternal and neonatal complications are rising. The objective of this study is to determine the rate and indications for Cesarean section at King Abdullah University Hospital (KAUH) in Jordan and to assess the resulting neonatal outcomes. Methods A retrospective chart review was conducted for all women and neonates delivered by Cesarean section during the period January 2016 to July 2017 at KAUH tertiary academic center. Collected data include demographic characteristics, indication for delivery, and neonatal outcomes such as NICU admission, respiratory complications, sepsis, mortality, and length of hospitalization. Results Two thousand five hundred ninety-five Cesarean section deliveries were performed over 18 months representing a rate of 50.5% of all deliveries. Sixty percent were scheduled procedures. Seventy-two percent were performed at full term gestation. The most common indication was previously scarred uterus (42.8%) followed by fetal distress (15.5%). The rate of admission to the neonatal ICU was 30% (800/2595). After multilogistic conditional regression analysis, the factors associated with increased risk of neonatal ICU admission were found to include grandmultiparity (Adjusted OR 1.46), gestational diabetes (Adjusted OR 1.92), maternal employment (Adjusted OR 1.84), prolonged rupture of membranes (Adjusted OR 5), fetal distress (Adjusted OR 1.84), prematurity (Adjusted OR 43.78), low birth weight (Adjusted OR 42), high order multiple gestation (Adjusted OR 9.58) and low 5-min APGAR score (Adjusted OR 10). Among the babies electively delivered at early term (37–38.6 weeks), 16% were admitted to the NICU for a median length of stay of 4 days (IQR 2, 8). The most common diagnoses for admitted term neonates were transient tachypnea of newborns and respiratory distress syndrome. Conclusions CS deliveries account for more than half the number of deliveries at our institution and almost one third of the delivered babies are admitted to the NICU. Together with the resulting maternal and neonatal consequences, this carries a major burden on the newborns, health care facilities, and involved families. Local strategies and policies should be established and implemented to improve the outcome of births.

Background: The education and training of healthcare workers (HCWs) about pandemic response plans, infection control protocols (ICP), and precautions are critical for breaking the virus transmission chain. This study aimed to assess the knowledge of HCWs regarding the COVID-19 pandemic response plan and the ICP. Concomitantly, evaluating the effectiveness and impact of institutional measures, policies, and training programs. Methods: A cross-sectional study using an electronic questionnaire was used to collect data from 267 HCWs at a University-affiliated-hospital during April 2020. Results: In this study, 90.7% of participants were nurses and 66% were females. 60.3% of participants received specific training about caring for COVID-19 patients while at least 94.3% reviewed the pandemic response plan and ICP for COVID-19. 47.5% and 29.2% of participants provided direct care for suspected or confirmed COVID-19 patients, respectively. Between 85.7% and 100% of the participants answered all items correctly regarding the COVID-19 pandemic response plan, measures, and precautions. Furthermore, the correct answers were above 95% for each item. Conclusion: HCWs have a high level of knowledge about the COVID-19 pandemic response plan and ICP. Training and disseminating updated plans and protocols in different methods such as an intranet and onsite training in addition to regular methods were very effective.

In March 2020, a wedding in Jordan led to a large outbreak of coronavirus disease (COVID-19). We collected data on 350 wedding attendees, 76 who of whom developed COVID-19. Our study shows high communicability of COVID-19 and the enormous risk for severe acute respiratory syndrome 2 virus transmission during mass gatherings.

Background: Sepsis in the neonatal intensive care unit (NICU) remains one of the most significant causes of morbidity and mortality, especially for preterm newborns. Multi-drug resistant organisms (MDROs) are emerging as important pathogens that cause neonatal sepsis in NICU. Therefore, studying the epidemiology, clinical features, and outcome caused by MDROs vs. non-MDROs, and identifying risk factors that may predispose patients to sepsis by MDROs are important. Methods: Episodes of blood culture-proven sepsis (age: 0–90 days) in the NICU at our institution from January 2012 to December 2015 were retrospectively reviewed. Collected data included demographics, signs at time of sepsis, laboratory values, microbiologic results, and final outcome. We compared clinical and laboratory data and final outcome for patients with sepsis due to MDROs vs. non-MDROs. Multivariate analysis was performed on variables with a P value of

Introduction: The decision to terminate a pregnancy due to fetal anomalies can have a significant emotional impact, especially in second-trimester terminations. Previous studies on the psychological consequences of pregnancy termination have had limitations, and little is known about the outcomes for partners and the impact of fetal donation. Therefore, we aimed to investigate the psychological effects of second-trimester pregnancy termination and identify factors associated with outcomes in both women and men, including donation of fetal remains to science., Material and Methods: A longitudinal cohort study was conducted at the Amsterdam UMC in the Netherlands, involving women and partners who underwent termination at or before 23 weeks and 6 days of gestation. Questionnaires were administered at termination, 6 weeks, and 4 months after. We utilized validated questionnaires to assess psychological morbidity (grief, post-traumatic stress and postnatal depression and quality of life [QoL]), and factors that could potentially influence outcomes., Results: Of 241 participants, women displayed more pronounced psychological distress than men, though both groups improved over time. Four months after termination, 27.4% of women and 9.1% of men showed signs of pathological grief. Scores indicative for postnatal depression occurred in 19.8% women and 4.1% of men. A prior psychiatric history was a consistent predictor of poorer outcomes. Fetal donation to the Dutch Fetal Biobank was associated with reduced likelihood of symptoms of complicated grief four months after termination., Conclusions: Second-trimester termination of pregnancy for fetal anomalies can lead to psychological morbidity, particularly in women. However, there is a notable improvement over time for both groups. Individuals with prior psychiatric history appear more vulnerable post-termination. Also, fetal donation to science did not have a negative impact on psychological well-being., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Prenatal ultrasound is widely used to screen for structural anomalies before birth. While this is traditionally done in the second trimester, there is an increasing use of first-trimester ultrasound for early detection of lethal and certain severe structural anomalies., Objectives: To evaluate the diagnostic accuracy of ultrasound in detecting fetal structural anomalies before 14 and 24 weeks' gestation in low-risk and unselected pregnant women and to compare the current two main prenatal screening approaches: a single second-trimester scan (single-stage screening) and a first- and second-trimester scan combined (two-stage screening) in terms of anomaly detection before 24 weeks' gestation., Search Methods: We searched MEDLINE, EMBASE, Science Citation Index Expanded (Web of Science), Social Sciences Citation Index (Web of Science), Arts & Humanities Citation Index and Emerging Sources Citation Index (Web of Science) from 1 January 1997 to 22 July 2022. We limited our search to studies published after 1997 and excluded animal studies, reviews and case reports. No further restrictions were applied. We also screened reference lists and citing articles of each of the included studies., Selection Criteria: Studies were eligible if they included low-risk or unselected pregnant women undergoing a first- and/or second-trimester fetal anomaly scan, conducted at 11 to 14 or 18 to 24 weeks' gestation, respectively. The reference standard was detection of anomalies at birth or postmortem., Data Collection and Analysis: Two review authors independently undertook study selection, quality assessment (QUADAS-2), data extraction and evaluation of the certainty of evidence (GRADE approach). We used univariate random-effects logistic regression models for the meta-analysis of sensitivity and specificity., Main Results: Eighty-seven studies covering 7,057,859 fetuses (including 25,202 with structural anomalies) were included. No study was deemed low risk across all QUADAS-2 domains. Main methodological concerns included risk of bias in the reference standard domain and risk of partial verification. Applicability concerns were common in studies evaluating first-trimester scans and two-stage screening in terms of patient selection due to frequent recruitment from single tertiary centres without exclusion of referrals. We reported ultrasound accuracy for fetal structural anomalies overall, by severity, affected organ system and for 46 specific anomalies. Detection rates varied widely across categories, with the highest estimates of sensitivity for thoracic and abdominal wall anomalies and the lowest for gastrointestinal anomalies across all tests. The summary sensitivity of a first-trimester scan was 37.5% for detection of structural anomalies overall (95% confidence interval (CI) 31.1 to 44.3; low-certainty evidence) and 91.3% for lethal anomalies (95% CI 83.9 to 95.5; moderate-certainty evidence), with an overall specificity of 99.9% (95% CI 99.9 to 100; low-certainty evidence). Two-stage screening had a combined sensitivity of 83.8% (95% CI 74.7 to 90.1; low-certainty evidence), while single-stage screening had a sensitivity of 50.5% (95% CI 38.5 to 62.4; very low-certainty evidence). The specificity of two-stage screening was 99.9% (95% CI 99.7 to 100; low-certainty evidence) and for single-stage screening, it was 99.8% (95% CI 99.2 to 100; moderate-certainty evidence). Indirect comparisons suggested superiority of two-stage screening across all analyses regarding sensitivity, with no significant difference in specificity. However, the certainty of the evidence is very low due to the absence of direct comparisons., Authors' Conclusions: A first-trimester scan has the potential to detect lethal and certain severe anomalies with high accuracy before 14 weeks' gestation, despite its limited overall sensitivity. Conversely, two-stage screening shows high accuracy in detecting most fetal structural anomalies before 24 weeks' gestation with high sensitivity and specificity. In a hypothetical cohort of 100,000 fetuses, the first-trimester scan is expected to correctly identify 113 out of 124 fetuses with lethal anomalies (91.3%) and 665 out of 1776 fetuses with any anomaly (37.5%). However, 79 false-positive diagnoses are anticipated among 98,224 fetuses (0.08%). Two-stage screening is expected to correctly identify 1448 out of 1776 cases of structural anomalies overall (83.8%), with 118 false positives (0.1%). In contrast, single-stage screening is expected to correctly identify 896 out of 1776 cases before 24 weeks' gestation (50.5%), with 205 false-positive diagnoses (0.2%). This represents a difference of 592 fewer correct identifications and 88 more false positives compared to two-stage screening. However, it is crucial to acknowledge the uncertainty surrounding the additional benefits of two-stage versus single-stage screening, as there are no studies directly comparing them. Moreover, the evidence supporting the accuracy of first-trimester ultrasound and two-stage screening approaches primarily originates from studies conducted in single tertiary care facilities, which restricts the generalisability of the results of this meta-analysis to the broader population., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Small intestine (SI) maturation during early life is pivotal in preventing the onset of gut diseases. In this study we interrogated the milestones of SI development by gene expression profiling and ingenuity pathway analyses. We identified a set of cytokines as main regulators of changes observed across different developmental stages. Upon cytokines stimulation, with IFNγ as the most contributing factor, human fetal organoids (HFOs) increase brush border gene expression and enzyme activity as well as trans -epithelial electrical resistance. Electron microscopy revealed developed brush border and loss of fetal cell characteristics in HFOs upon cytokine stimulation. We identified T cells as major source of IFNγ production in the fetal SI lamina propria. Co-culture of HFOs with T cells recapitulated the major effects of cytokine stimulation. Our findings underline pro-inflammatory cytokines derived from T cells as pivotal factors inducing functional SI maturation in vivo and capable of modulating the barrier maturation of HFOs in vitro ., Competing Interests: J.-N.B. is an employee of DNAnexus. I.B.R. is an employee of Danone Nutricia Research., (© 2024 The Authors.)

Objectives: Down syndrome (DS) is associated with airway abnormalities including a narrowed trachea. It is uncertain whether this narrowed trachea in DS is a consequence of deviant fetal development or an acquired disorder following endotracheal intubation after birth. This study aimed to compare the tracheal morphology in DS and non-DS fetuses using microfocus computed tomography (micro-CT)., Methods: Twenty fetal samples were obtained from the Dutch Fetal Biobank and divided into groups based on gestational age. Micro-CT images were processed to analyze tracheal length, volume, and cross-sectional area (CSA)., Results: Mean tracheal length and tracheal volume were similar in DS and non-DS fetuses for all gestational age groups. Mean, minimum, and maximal tracheal CSA were statistically significantly increased in the single DS fetus in the group of 21-24 weeks of gestation, but not in other gestational age groups. In 90% of all studied fetuses, the minimum tracheal CSA was located in the middle third of the trachea., Conclusion: Tracheal development in DS fetuses was similar to non-DS fetuses between 13 and 21 weeks of gestation. This suggests that the narrowed tracheal diameter in DS children may occur later in fetal development or results from postnatal intubation trauma. The narrowest part of the trachea is in majority of DS and non-DS fetuses the middle third., Level of Evidence: Level 3 Laryngoscope, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Recent studies of human embryos and fetuses have advanced our understanding not only of basic biology but also of health and disease, through a combination of detailed three-dimensional (3D) morphology and processes such as gene expression, cellular decision-making and differentiation, and epigenetics during the various phases of human development and growth. Large-scale research initiatives focusing on these topics have been initiated during the last decade, all of which depend on biobanks that provide high-quality images of human embryonic and fetal morphology, as well as on high-quality collections of tissue samples that are obtained and stored appropriately. In this perspective, we describe our experience in establishing the Dutch Fetal Biobank to present the framework and workflow of the biobank, provide a brief discussion of the main legal and ethical aspects involved in establishing a pre-natal tissue bank, and present the preliminary data on the first 329 donated specimens., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study aimed to assess the feasibility of postmortem ultra-high-field magnetic resonance imaging (UHF-MRI) to study fetal musculoskeletal anatomy and explore the contribution of variation in iodine and formaldehyde (paraformaldehyde, PFA) treatment of tissue., Methods: Seven upper extremities from human fetuses with gestational ages of 19 to 24 weeks were included in this experimental study, approved by the Medical Research Ethics Committee. The specimens were treated with various storage (0.2-4% PFA) and staining (Lugol's solution) protocols and the wrist joint was subsequently imaged with 7.0 T UHF-MRI. Soft-tissue contrast was quantified by determining regions of interest within a chondrified carpal bone (CCB) from the proximal row, the triangular fibrocartilage (TFC), and the pronator quadratus muscle (PQM) and calculating the contrast ratios (CRs) between mean signal intensities of CCB to TFC and CCB to PQM., Results: UHF-MRI showed excellent soft-tissue contrast in different musculoskeletal tissues. Increasing storage time in 4% PFA, CRs decreased, resulting in a shift from relatively hyperintense to hypointense identification of the CCB. Storage in 0.2% PFA barely influenced the CRs over time. Lugol's solution caused an increase in CRs and might have even contributed to the inversion of the CRs., Conclusions: UHF-MRI is a feasible technique to image musculoskeletal structures in fetal upper extremities and most successful after short storage in 4% PFA or prolonged storage in 0.2% PFA. The use of Lugol's solution is not detrimental on soft-tissue MRI contrast and therefore enables effectively combining UHF-MRI with contrast-enhanced micro-computed tomography using a single preparation of the specimen., Relevance Statement: UHF-MRI can be performed after CE-micro-CT to take advantage of both techniques., Key Points: • UHF-MRI is feasible to study human fetal cartilaginous and ligamentous anatomy. • Storage in low PFA concentrations (i.e., 0.2%) improves soft-tissue contrast in UHF-MRI. • Limited preservation time in high concentrations of PFA improves soft-tissue contrast in UHF-MRI. • Prior staining with Lugol's solution does not reduce soft-tissue contrast in UHF-MRI., (© 2023. The Author(s).)

Over the last few years, fetal postmortem microfocus computed tomography (micro-CT) imaging has increased in popularity for both diagnostic and research purposes. Micro-CT imaging could be a substitute for autopsy, particularly in very early gestation fetuses for whom autopsy can be technically challenging and is often unaccepted by parents. This article provides an overview of the latest research in fetal postmortem micro-CT imaging with a focus on diagnostic accuracy, endovascular staining approaches, placental studies and the reversibility of staining. It also discusses new methods that could prove helpful for micro-CT of larger fetuses. While more research is needed, contrast-enhanced micro-CT has the potential to become a suitable alternative to fetal autopsy. Further research using this novel imaging tool could yield wider applications, such as its practise in imaging rare museum specimens., (© 2022. The Author(s).)

Objectives: Adult spleens show extensive morphological variation, with a reported prevalence of 40-98% clefts (also called notches or fissures) on the splenic surface and 10-30% accessory spleens at autopsy. It is hypothesised that both anatomical variants result from a complete or partial failure of multiple splenic primordia to fuse to the main body. According to this hypothesis, fusion of the spleen primordia is completed after birth and spleen morphological variations are often explained as stagnation of spleen development at the foetal stage. We tested this hypothesis by studying early spleen development in embryos, and compared foetal and adult spleen morphology., Methods and Materials: We assessed 22 embryonic, 17 foetal and 90 adult spleens on the presence of clefts using histology, micro-CT and conventional post-mortem CT-scans, respectively., Results: The spleen primordium was observed as a single mesenchymal condensation in all embryonic specimens. The number of clefts varied from 0 to 6 in foetuses, compared to 0-5 in adults. We found no correlation between foetal age and number of clefts (R 2 = 0.004). The independent samples Kolmogorov-Smirnov test showed no significant difference in the total number of clefts between adult and foetal spleens ( p = 0.068)., Conclusion: We found no morphological evidence for a multifocal origin or a lobulated developmental stage of the human spleen., Advances in Knowledge: Our findings show that splenic morphology is highly variable, independent of developmental stage and age. We suggest to abandon the term "persistent foetal lobulation" and to regard splenic clefts, regardless of their number or location, as normal variants.

Due to advancements in ultrasound techniques, the focus of antenatal ultrasound screening is moving towards the first trimester of pregnancy. The early first trimester however remains in part, a 'black box', due to the size of the developing embryo and the limitations of contemporary scanning techniques. Therefore there is a need for images of early anatomical developmental to improve our understanding of this area. By using new imaging techniques, we can not only obtain better images to further our knowledge of early embryonic development, but clear images of embryonic and fetal development can also be used in training for e.g. sonographers and fetal surgeons, or to educate parents expecting a child with a fetal anomaly. The aim of this review is to provide an overview of the past, present and future techniques used to capture images of the developing human embryo and fetus and provide the reader newest insights in upcoming and promising imaging techniques. The reader is taken from the earliest drawings of da Vinci, along the advancements in the fields of in utero ultrasound and MR imaging techniques towards high-resolution ex utero imaging using Micro-CT and ultra-high field MRI. Finally, a future perspective is given about the use of artificial intelligence in ultrasound and new potential imaging techniques such as synchrotron radiation-based CT to increase our knowledge regarding human development., Competing Interests: Declarations of interest Yousif Dawood, Johannes A. Smit, Jaco Hagoort, Karl Jacobs, Roelof-Jan Oostra: none. Marieke F.J. Buijtendijk, Bernadette S. de Bakker and Maurice J.B. van den Hoff receive funding from a Dutch Top Sector Life Sciences & Health Consortium grant to investigate visualization of fetal anatomical structures by three-dimensional ultrasound. Samsung Medison (South Korea) supports the research in three-dimensional ultrasound through the loan of ultrasound equipment and partial coverage of the salary costs for the first year of the study. Marieke F.J. Buijtendijk received payment from NeuroLogica Corporation to present in a webinar on first trimester three-dimensional ultrasound imaging. Maurice J. B. van den Hoff is chair of the European Society of Cardiology, Working Group on Development, Anatomy and Pathology. Harsha Shah: receives honoraria for lecturing and research funding from Samsung Medison (South Korea). Tom Bourne receives honoraria for lecturing and research funding from Samsung Medison (South Korea), research support from Roche Diagnostics (Switzerland) and research support from Illumina, Inc (USA). He is supported by the NIHR Biomedical Research Center based at Imperial College Healthcare NHS Trust and Imperial College London., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Male hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated metabolism, particularly in the small intestine. The aim of this work was to examine the esterase-inhibitory effect of natural fruit extract of strawberry (STW) on the intestinal degradation of TU as a potential approach to increasing the oral bioavailability of T. Herein, the hydrolysis of TU was assessed in fasted state simulated intestinal fluid with added esterase activity (FaSSIF/ES) and Caco-2 cell homogenates in the presence of STW extract. It is noteworthy that STW substantially inhibited the degradation of TU in FaSSIF/ES and Caco-2 cell homogenates at concentrations that could be achieved following oral consumption of less than one serving of STW fruit. This can significantly increase the fraction of unhydrolyzed TU in the intestinal lumen as well as in enterocytes. In addition, it was demonstrated that TU has high intestinal lymphatic transport potential as the association of TU with plasma-derived human chylomicrons was in the range of 84%. Therefore, oral co-administration of TU with STW could potentially increase the intestinal stability of TU and consequently the contribution of lymphatically delivered TU to the systemic exposure of T in vivo.

Mitchell-Riley syndrome (MRS) is caused by recessive mutations in the regulatory factor X6 gene ( RFX6 ) and is characterised by pancreatic hypoplasia and neonatal diabetes. To determine why individuals with MRS specifically lack pancreatic endocrine cells, we micro-CT imaged a 12-week-old foetus homozygous for the nonsense mutation RFX6 c.1129C>T, which revealed loss of the pancreas body and tail. From this foetus, we derived iPSCs and show that differentiation of these cells in vitro proceeds normally until generation of pancreatic endoderm, which is significantly reduced. We additionally generated an RFX6 HA reporter allele by gene targeting in wild-type H9 cells to precisely define RFX6 expression and in parallel performed in situ hybridisation for RFX6 in the dorsal pancreatic bud of a Carnegie stage 14 human embryo. Both in vitro and in vivo , we find that RFX6 specifically labels a subset of PDX1-expressing pancreatic endoderm. In summary, RFX6 is essential for efficient differentiation of pancreatic endoderm, and its absence in individuals with MRS specifically impairs formation of endocrine cells of the pancreas head and tail., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)