The duration of embryo culture after mouse IVF differentially affects cardiovascular and metabolic health in male offspring.

STUDY QUESTION: Do the long-term health outcomes following IVF differ depending upon the duration of embryo culture before transfer? SUMMARY ANSWER: Using a mouse model, we demonstrate that in male but not female offspring, adverse cardiovascular (CV) health was more likely with prolonged culture to the blastocyst stage, but metabolic dysfunction was more likely if embryo transfer (ET) occurred at the early cleavage stage. WHAT IS KNOWN ALREADY: ART associate with increased risk of adverse CV and metabolic health in offspring, and these findings have been confirmed in animal models in the absence of parental infertility issues. It is unclear which specific ART treatments may cause these risks. There is increasing use of blastocyst, versus cleavage-stage, transfer in clinical ART which does not appear to impair perinatal health of children born, but the longer-term health implications are unknown. STUDY DESIGN, SIZE, DURATION: Five mouse groups were generated comprising: (i) natural mating (NM)-naturally mated, non-superovulated and undisturbed gestation; (ii) IV-ET-2Cell-in-vivo derived two-cell embryos collected from superovulated mothers, with immediate ET to recipients; (iii) IVF-ET-2Cell-IVF generated embryos, from oocytes from superovulated mothers, cultured to the two-cell stage before ET to recipients; (iv) IV-ET-BL-in-vivo derived blastocysts collected from superovulated mothers, with immediate ET to recipients; (v) IVF-ET-BL-IVF generated embryos, from oocytes from superovulated mothers, cultured to the blastocyst stage before ET to recipients. Both male and female offspring were analysed for growth, CV and metabolic markers of health. There were 8-13 litters generated for each group for analyses; postnatal data were analysed by multilevel random effects regression to take account of between-mother and within-mother variation and litter size. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: C57/BL6 female mice (3-4 weeks old) were used for oocyte production; CBA males for sperm with human tubal fluid medium were used for IVF. Embryos were transferred (ET) to MF1 pseudo-pregnant recipients at the two-cell stage or cultured in synthetic oviductal medium enriched with potassium medium to the blastocyst stage before ET. Control in-vivo embryos from C57BL6 × CBA matings were collected and immediately transferred at the two-cell or blastocyst stage. Postnatal assays included growth rate up to 27 weeks; systolic blood pressure (SBP) at 9, 15 and 21 weeks; lung and serum angiotensin-converting enzyme (ACE) activity at time of cull (27 weeks); glucose tolerance test (GTT; 27 weeks); basal glucose and insulin levels (27 weeks); and lipid accumulation in liver cryosections using Oil Red O imaging (27 weeks). MAIN RESULTS AND THE ROLE OF CHANCE: Blastocysts formed by IVF developed at a slower rate and comprised fewer cells that in-vivo generated blastocysts without culture (P < 0.05). Postnatal growth rate was increased in all four experimental treatments compared with NM group (P < 0.05). SBP, serum and lung ACE and heart/body weight were higher in IVF-ET-BL versus IVF-ET-2Cell males (P < 0.05) and higher than in other treatment groups, with SBP and lung ACE positively correlated (P < 0.05). Glucose handling (GTT AUC) was poorer and basal insulin levels were higher in IVF-ET-2Cell males than in IVF-ET-BL (P < 0.05) with the glucose:insulin ratio more negatively correlated with body weight in IVF-ET-2Cell males than in other groups. Liver/body weight and liver lipid droplet diameter and density in IVF-ET-2Cell males were higher than in IVF-ET-BL males (P < 0.05). IVF groups had poorer health characteristics than their in-vivo control groups, indicating that outcomes were not caused specifically by background techniques (superovulation, ET). No consistent health effects from duration of culture were identified in female offspring. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models, in this case, in the absence of confounding parental infertility, in assessing the safety of ART manipulations. WIDER IMPLICATIONS OF THE FINDINGS: The study indicates that longer duration of embryo culture after IVF up to blastocyst before ET leads to increased dysfunction of CV health in males compared with IVF and shorter cleavage-stage ET. However, the metabolic health of male offspring was poorer after shorter versus longer culture duration. This distinction indicates that the origin of CV and metabolic health phenotypes after ART may be different. The poorer metabolic health of males after cleavage-stage ET coincides with embryonic genome activation occurring at the time of ET. STUDY FUNDING/COMPETING INTEREST(S): This work was supported through the European Union FP7-CP-FP Epihealth programme (278418) and FP7-PEOPLE-2012-ITN EpiHealthNet programme (317146) to T.P.F., the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/F007450/1) to T.P.F., and the Saudi government, University of Jeddah and King Abdulaziz University to A.A. The authors have no conflicts of interest to declare.

Deferent Anatomical Presentations of Iliolumbar Ligament: A Cadaveric Study.

This work was carried out to describe the detailed gross anatomy of the iliolumbar ligaments in human cadavers and to shed more light on these disputes regarding the configuration and direction of these ligaments. Twenty partially dissected human formalin-preserved cadavers originating from North America and Europe were investigated in this study. Blunt dissection was made through the ventral and dorsal aspects of the pelvic area of the cadavers. According to the current study, the anterior and posterior portions of the iliolumbar ligament most frequently attached to the 5th lumbar vertebra's transverse process (70% and 80%, respectively). The body of the 4th lumbar vertebra with the 5th lumbar vertebra' transverse process was the attachment of the anterior part (30%). The attachment of the posterior part was the body of the 5th lumbar vertebra (20%). The anterior and posterior parts of the iliolumbar ligament were inserted into the anterior tip of the iliac crest. There is an obvious variation in the morphological appearance of the iliolumbar ligament distinguished in attachments, length, width, thickness, number of bands, and the presence of accessory bands in the anterior part of the ligament. In addition, a new attachment for the anterior band was revealed in one-third of the specimens (body of the 4th lumbar vertebra) which have not been described before. Also, in one-fifth of the specimens, there was a new attachment for the posterior band (body of the 5th lumbar vertebra).

Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk.

Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the 'Developmental Origins of Health and Disease' (DOHaD) concept. In this review, we consider the effects of maternal undernutrition experienced during the peri-conception period in select human models and in a mouse experimental model of protein restriction. Human datasets indicate that macronutrient deprivation around conception affect the epigenome, with enduring effects on cardiometabolic and neurological health. The mouse model, comprising maternal low protein diet exclusively during the peri-conception period, has revealed a stepwise progression in altered developmental programming following induction through maternal metabolite deficiency. This progression includes differential effects in extra-embryonic and embryonic cell lineages and tissues, leading to maladaptation in the growth trajectory and increased chronic disease comorbidities. The timeline embraces an array of mechanisms across nutrient sensing and signalling, cellular, metabolic, epigenetic and physiological processes with a coordinating role for mTORC1 signalling proposed. Early embryos appear active participants in environmental sensing to optimise the developmental programme for survival but with the trade-off of later disease. Similar adverse health outcomes may derive from other peri-conception environmental experiences, including maternal overnutrition, micronutrient availability, pollutant exposure and assisted reproductive treatments (ART) and support the need for preconception health before pregnancy.

Investigating healthcare practitioners' attitudes towards the COVID-19 outbreak in Saudi Arabia: A general qualitative framework for managing the pandemic.

BACKGROUND: Some previous studies have investigated the attitudes of healthcare professionals towards certain aspects of the COVID-19 outbreak. In addition, some general frameworks have been proposed to manage the pandemic. OBJECTIVE: The purpose of this article was to analyze the attitudes of healthcare practitioners in Saudi Arabia towards the treatment of patients with COVID-19, work planning of practitioners, leadership approaches to manage the pandemic, sharing information strategies, medical errors, compliance with procedures, and challenges faced by the practitioners. Furthermore, another objective was to propose a general framework for managing the COVID-19 outbreak in Saudi Arabia. METHODS: To achieve these purposes, a survey was designed based on an online questionnaire that was initially sent via WhatsApp, Twitter, Facebook, and email to 336 healthcare practitioners working in 7 hospitals in Saudi Arabia. The response rate was 30.4%. RESULTS: The outcomes indicated that healthcare practitioners in Saudi Arabia had positive attitudes towards effective communication and interaction between health professionals and patients, leadership and maintenance of team coordination, work planning, communication and cooperation between team members, training and skills development of healthcare professionals, implementing strict procedures to avoid errors and control the spread of the COVID-19 pandemic, maintaining an adequate supply of medicines and medical equipment, and obtaining the support of the government, the community, and the people. CONCLUSION: Based on the findings, it was possible to suggest that the management of health care operations related to the COVID-19 outbreak in Saudi Arabia requires effective collaboration and information sharing among various stakeholders. In this sense, communication, effective leadership, coordination and work planning, adequate treatment for patients, strict compliance with hospital rules and procedures, preventive and regulatory measures, and training and support for health professionals, were parameters considered in the general qualitative framework suggested in this study for managing the COVID-19 pandemic in Saudi Arabia. The propositions presented in this study can help the Saudi Arabian government implement an effective plan to control the spread of the COVID-19 pandemic in this country.

Implications of Public Understanding of COVID-19 in Saudi Arabia for Fostering Effective Communication Through Awareness Framework.

Background: Participation of the public is an important and most effective approach for controlling the spread of novel coronavirus. However, considering its novel nature, it is important to create awareness among the public to be able to take timely preventive measures. On the contrary, misinformation and myths from online communities result in severe damages in mitigation of this novel disease. Objective: Focusing on these aspects, this manuscript reviews public awareness about COVID-19, myths surrounding it, its symptoms, treatment, transmission, importance of information sources, types of information to be considered in awareness campaigns, promotional channels, and their implications in Saudi Arabia. Methods: An online questionnaire-based survey was used for collecting data related to five major aspects related to COVID-19 and awareness creation process. The survey was accessed by 1,881 people, out of whom 741 people participated in the survey. However, 150 dropouts left the survey in between, as a result of which a final sample of 591 was achieved, indicating the response rate of 39.3% and a completion rate of 79.76%. Results: Awareness levels of the participants related to COVID-19, its means of transmission, preventive measures, symptoms, and treatment were identified to be moderate to high (60-80%). However, reliance on a few myths and violation of certain preventive measures were identified with majority of the participants (more than 60%). The Ministry of Health was identified to be the most reliable source of information followed by family and friends. Moreover, 15 types of information were identified to be highly relevant and important, which need to be effectively disseminated among the public through effective communication channels. Conclusions: Lack of awareness can result in serious outcomes in relation to COVID-19. Effective awareness campaigns including relevant information from reliable sources can improve the knowledge of people, and they must be effective in developing positive attitudes among the public toward adopting preventive measures.

A Comparative Study on the Strategies Adopted by the United Kingdom, India, China, Italy, and Saudi Arabia to Contain the Spread of the COVID-19 Pandemic.

PURPOSE: The objective of this study was to compare the strategies adopted by the United Kingdom, Italy, China, India, and Saudi Arabia to contain the spread of the COVID-19 pandemic. MATERIALS AND METHODS: A review of the literature was carried out to collect data on the strategies used by China, Italy, India, the United Kingdom, and Saudi Arabia to contain the spread of the COVID-19 virus. The global analysis of 65 published literature references allowed observing the effectiveness and efficiency of the strategies used by these countries to control the spread of the COVID-19 virus. RESULTS: Both mitigation and suppression strategies were adopted by the United Kingdom, India, Italy, China, and Saudi Arabia to control the spread of the COVID-19 pandemic. It was observed that China has achieved a greater success in flattening the curve compared to the other countries. In China, few new daily cases have occurred since March, and it has been the only country that has managed to keep the COVID-19 pandemic under control. On the other hand, reductions in the number of daily cases (since May 2020) were detected in the United Kingdom, Italy, and Saudi Arabia (since July 2020). Also, during the last 3 months (June, July and August) India has shown the highest growth in the total number of confirmed cases and in the number of new daily cases, compared to the mentioned countries. CONCLUSION: The review of the strategies adopted by China, India, the United Kingdom, Italy and Saudi Arabia to combat the COVID-19 pandemic can guide countries in the design and development of mitigation and suppression approaches to control the spread of the COVID-19 virus. Containment strategies such as lockdowns cannot continue in the long term. Therefore, countries must adopt mitigation and prevention strategies to protect people from infection and learn to live with the virus.