Growth Based Morphogenesis of Vertebrate Limb Bud

Many genes and their regulatory relationships are involved in developmental phenomena. However, by chemical information alone, we cannot fully understand changing organ morphologies through tissue growth because deformation and growth of the organ are essentially mechanical processes. Here, we develop a mathematical model to describe the change of organ morphologies through cell proliferation. Our basic idea is that the proper specification of localized volume source (e.g., cell proliferation) is able to guide organ morphogenesis, and that the specification is given by chemical gradients. We call this idea “growth-based morphogenesis.” We find that this morphogenetic mechanism works if the tissue is elastic for small deformation and plastic for large deformation. To illustrate our concept, we study the development of vertebrate limb buds, in which a limb bud protrudes from a flat lateral plate and extends distally in a self-organized manner. We show how the proportion of limb bud shape depends on different parameters and also show the conditions needed for normal morphogenesis, which can explain abnormal morphology of some mutants. We believe that the ideas shown in the present paper are useful for the morphogenesis of other organs

Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections

AbstractBackgroundAsymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures.MethodsUsing reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever &gt;= 37.5°C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment.ResultsBased on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6th July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of the 7th June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI: 5.6% – 24%) (Belgium).ConclusionsWe found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country’s population infected with SARS-CoV-2 worldwide is generally low.FundingWellcome Trust, Bill &amp; Melinda Gates Foundation, DFID, NIHR, GCRF, ARC.</jats:sec

Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections

Background: Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures. Methods: Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever ≥ 37.5 °C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment. Results: Based on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6 July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of 7 June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI 5.6–24%) (Belgium). Conclusions: We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country’s population infected with SARS-CoV-2 worldwide is generally low

Relaxin-2 during pregnancy according to glycemia, continence status, and pelvic floor muscle function

Introduction and hypothesis: To investigate relaxin-2 concentration comparing gestational diabetes mellitus (GDM) and non-GDM patients during pregnancy according to urinary incontinence (UI) and pelvic function status. Methods: This is a cross-sectional study evaluating 282 pregnant women from 24 weeks of gestation. The participants were divided into two groups, non-GDM and GDM, according to American Diabetes Association’s diabetes mellitus gestational threshold. In addition, according to subanalysis, both groups were subdivided according to the presence of pregnancy-specific urinary incontinence: non-GDM continent, non-GDM incontinent, GDM continent, and GDM incontinent. All participants filled in questionnaires on clinical, obstetric, and urinary continence status (International Consultation on Incontinence Questionnaire-Short Form, ICIQ-SF, and Incontinence Severity Index, ISI), followed by pelvic floor muscle evaluation by the PERFECT scheme in which strength, endurance, and speed of contractions were evaluated. Results: Serum relaxin-2 concentrations were significantly lower in pregnant women with pregnancy-specific urinary incontinence in both non-GDM and GDM patients, but GDM showed the lowest concentration. In addition, the stratification of the groups according to pelvic floor muscle strength showed that pregnant patients with GDM and modified Oxford scale 0–2 had significantly lower levels than those who were non-GDM and GDM with Modified Oxford Scale 3–5. Relaxin-2 level was much lower in GDM incontinent pregnant women with MOS 0–2 compared to the other three groups. Conclusions: Lower relaxin-2 concentration was associated with the presence of pregnancy-specific urinary incontinence, but the combination of GDM, pregnancy-specific urinary incontinence, and lower levels of pelvic floor strength led to lower levels of relaxin-2 compared to the other three groups.Postgraduate Program on Tocogynecology São Paulo State University (UNESP), BotucatuSchool of Rehabilitation Sciences Faculty of Health Sciences University of OttawaDepartment of Physical Education Institute of Biosciences of Rio Claro São Paulo State University (UNESP), Rio ClaroPostgraduate Program on Tocogynecology São Paulo State University (UNESP), BotucatuDepartment of Physical Education Institute of Biosciences of Rio Claro São Paulo State University (UNESP), Rio Clar

Reversal of diabetic-induced myopathy by swimming exercise in pregnant rats:a translational intervention study

Gestational diabetes mellitus (GDM) plus rectus abdominis muscle (RAM) myopathy predicts long-term urinary incontinence (UI). Atrophic and stiff RAM are characteristics of diabetes-induced myopathy (DiM) in pregnant rats. This study aimed to determine whether swimming exercise (SE) has a therapeutic effect in mild hyperglycemic pregnant rats model. We hypothesized that SE training might help to reverse RAM DiM. Mild hyperglycemic pregnant rats model was obtained by a unique subcutaneous injection of 100 mg/kg streptozotocin (diabetic group) or citrate buffer (non-diabetic group) on the first day of life in Wistar female newborns. At 90 days of life, the rats are mated and randomly allocated to remain sedentary or subjected to a SE protocol. The SE protocol started at gestational day 0 and consisted of 60 min/day for 6 days/week in a period of 20 days in a swim tunnel. On day 21, rats were sacrificed, and RAM was collected and studied by picrosirius red, immunohistochemistry, and transmission electron microscopy. The SE protocol increased the fiber area and diameter, and the slow-twitch and fast-twitch fiber area and diameter in the diabetic exercised group, a finding was also seen in control sedentary animals. There was a decreased type I collagen but not type III collagen area and showed a similar type I/type III ratio compared with the control sedentary group. In conclusion, SE during pregnancy reversed the RAM DiM in pregnant rats. These findings may be a potential protocol to consider in patients with RAM damage caused by GDM