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Background: There is limited evidence regarding optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus., Objective: This study aimed to examine the association between gestational weight gain and perinatal outcomes among women with gestational diabetes mellitus and twin pregnancies and to explore the gestational weight gain targets by prepregnancy body mass index category., Study Design: A national population-based cohort study of twin pregnancies with gestational diabetes mellitus was conducted between 2014 and 2020. Women with gestational diabetes mellitus aged between 18 and 45 years with live-born twins without congenital malformations between 24 and 42 weeks of gestation were included in the analysis. Two approaches were used to determine the optimal gestational weight gain targets by body mass index category: an interquartile range method to calculate targets in low-risk gestational diabetes mellitus pregnancies and a logistic model method to identify the odds ratio targets at which a composite adverse outcome decreased., Results: Of 29,308 women with gestational diabetes mellitus and twin pregnancies, 8239 (28.1%) were normal-weight, 7626 (26.0%) were overweight, and 13,443 (45.9%) were obese. The continuous standardized gestational weight gain by 36 weeks was associated with preterm birth <36 weeks, large-for-gestational-age infants, small-for-gestational-age infants, and gestational hypertensive disorders. The interquartile range targets were 13.6 to 20.9 kg, 10.9 to 20.4 kg, and 7.7 to 17.7 kg for normal-weight, overweight, and obese women, respectively. The odds ratio targets were 14.1 to 20.0 kg, 12.1 to 16.0 kg, and 6.1 to 12.0 kg for normal-weight, overweight, and obese women, respectively. Gestational weight gain outside these targets was associated with preterm birth <36 weeks, large-for-gestational-age and small-for-gestational-age infants, and gestational hypertensive disorders, and exhibited significant population attributable fractions for preterm birth <36 weeks, large-for-gestational-age infants, and gestational hypertensive disorders across body mass index categories., Conclusion: Compared with the Institute of Medicine guidelines, more stringent gestational weight gain targets would be beneficial for improved perinatal outcomes in women with gestational diabetes mellitus and twin pregnancies., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The discovery of induced pluripotent stem cells and the ability to manufacture them using clinically compliant protocols has the potential to revolutionize the field of regenerative medicine. However, realizing this potential requires the development of processes that are reliable, reproducible, and cost-effective and that at the same time do not compromise the safety of the individuals receiving this therapy. In the present report, we discuss how cost reductions can be obtained using our experience with obtaining approval of biologic agents, autologous therapy, and the recent approval of cord blood banks. Significance: For therapy to be widely available, the cost of manufacturing stem cells must be reduced. The steps proposed in the present report, when implemented, have the potential to reduce these costs significantly., (©AlphaMed Press.)

The field of pluripotent stem cells (PSCs) is in a state of dynamic flux driven by significant advances in the derivation of specific phenotypes from embryonic stem cells, breakthroughs in somatic cell nuclear transfer, and dramatic improvements in generating induced PSCs using zero footprint methods. Spurred by these technological advances, companies have begun to plan clinical studies using human PSC derivatives manufactured in current Good Manufacturing Practice-compliant conditions. In the present review, we discuss the challenges in making these biological products, starting from tissue sourcing to the processes involved in manufacture, storage, and distribution. Additional challenges exist to meeting the regulatory requirements and keeping costs affordable. A model is described that has been proposed by the U.S. National Institutes of Health for reducing the costs and permitting flexibility and innovation by individual investigators. This model, combined with small adjustments in the regulatory processes tailored to address the unique properties of PSCs, has the potential of significantly accelerating the implementation of PSC-based cell therapy., (©AlphaMed Press.)

The phenomenal progress made in stem cell biology in the past few years has infused the field of regenerative medicine with a great deal of scientific enthusiasm. However, along with the excitement of discovery comes a new sense of translational urgency. The prospect of using embryonic and induced pluripotent stem cell tools and technologies to produce cell-based therapies and other treatments is no longer a distant dream; it is a very real opportunity that demands our attention today. As with most new fields, regenerative medicine has experienced some significant growing pains, and we have identified a number of key obstacles to progress. Given our role as the lead U.S. biomedical research agency and the world's largest supporter of medical research, the National Institutes of Health (NIH) has a responsibility to find ways to reduce or remove many of these obstacles and, consequently, has-and continues-to respond to these challenges in a variety of ways. In this brief essay, we will review our progress and highlight a new development: the founding of a Center for Regenerative Medicine on the NIH campus.

Pluripotent human embryonic stem (ES) cells hold remarkable therapeutic potential, but their use is fraught with moral, ethical, scientific, and political concerns. In this essay, I discuss how an odd combination of patent issues, presidential policy, market uncertainties, and evolving Food and Drug Administration regulations have together hindered the progress of ES cell research in the United States of America. This coalescence of issues is unique. I suggest that these factors explain why the United States has not been a dominant player in advancing ES research. I predict that small, noncontroversial changes would go far in ameliorating many of the roadblocks that now exist. Most of these changes would not require a change in policy or even action by the U.S. government; a simple clarification and definition would suffice. The reason these changes have met solid resistance is suggested to derive from financial rather than moral, ethical, or scientific issues.

Background: In order to compare the gene expression profiles of human embryonic stem cell (hESC) lines and their differentiated progeny and to monitor feeder contaminations, we have examined gene expression in seven hESC lines and human fibroblast feeder cells using Illumina bead arrays that contain probes for 24,131 transcript probes., Results: A total of 48 different samples (including duplicates) grown in multiple laboratories under different conditions were analyzed and pairwise comparisons were performed in all groups. Hierarchical clustering showed that blinded duplicates were correctly identified as the closest related samples. hESC lines clustered together irrespective of the laboratory in which they were maintained. hESCs could be readily distinguished from embryoid bodies (EB) differentiated from them and the karyotypically abnormal hESC line BG01V. The embryonal carcinoma (EC) line NTera2 is a useful model for evaluating characteristics of hESCs. Expression of subsets of individual genes was validated by comparing with published databases, MPSS (Massively Parallel Signature Sequencing) libraries, and parallel analysis by microarray and RT-PCR., Conclusion: we show that Illumina's bead array platform is a reliable, reproducible and robust method for developing base global profiles of cells and identifying similarities and differences in large number of samples.

Human embryonic stem cells (hESCs) offer a renewable source of a wide range of cell types for use in research and cell-based therapies. Characterizing these cells provides important information about their current state and affords relevant details for subsequent manipulations. For example, identifying genes expressed during culture, as well as their temporal expression order after passaging and conditions influencing the formation of all three germ layers may be helpful for the production of functional beta islet cells used in treating type I diabetes. Although several hESC lines have demonstrated karyotypic instability during extended time in culture, select variant lines exhibit characteristics similar to their normal parental lines. Such variant lines may be excellent tools and abundant sources of cells for pilot studies and in vitro differentiation research in which chromosome number is not a concern, similar to the role currently played by embryonal carcinoma cell lines. It is crucial that the cells be surveyed at a genetic and proteomic level during extensive propagation, expansion, and manipulation in vitro. Here we describe a comprehensive characterization of the variant hESC line BG01V, which was derived from the karyotypically normal, parental hESC line BG01. Our characterization process employs cytogenetic analysis, short tandem repeat and HLA typing, mitochondrial DNA sequencing, gene expression analysis using quantitative reverse transcription-polymerase chain reaction and microarray, assessment of telomerase activity, methylation analysis, and immunophenotyping and teratoma formation, in addition to screening for bacterial, fungal, mycoplasma, and human pathogen contamination.

As of August 2005, 22 human embryonic stem cell (hESC) lines listed on the National Institutes of Health (NIH) hESC Registry were being distributed to investigators. At a June 2005 meeting of NIH-supported hESC researchers, we proposed that a set of shared standards should be available in order to characterize the cells unambiguously in multiple laboratories. Here, we elaborate such a plan to identify a set of standard methods and to initiate collaborative efforts to validate the standards. The standard assays we propose should be comprehensive enough to ensure that hESC banks can provide a consistent and reliable product for NIH researchers, and inexpensive enough that individual laboratories can afford to use at least some of the methods routinely in their laboratories. We expect that as data accumulate and standards evolve, a core set of tests will become the norm for routine assessment of hESC cultures and that these tests will lay the groundwork for clinical applications of these cells.

Microcarcinoma (incidental, latent) of the prostate gland occurred with a frequency of 11.7% and at an age-adjusted incidence rate (world standard) of 40.6% per 1000 necropsies in the sampled black male population. The frequency of microcarcinoma of the prostate in black males in Washington, D.C., is essentially the same as the frequency of latent carcinoma in other ethnic groups and in other geographic areas. Of the patients studied clinically, fifty-one percent (51%) were in low stage (Stages I and II) disease; sixty-three percent (62.7%) had a well differentiated, Grade I, carcinoma of the prostate; and forty-two percent (42.4%) were in the 65-74 age group. Mean plasma testosterone and estrone levels were significantly higher in cancer patients than in age-matched hospitalized controls. The factor with the highest risk ratio was urinary tract symptoms occurring 10 years or longer before the onset of the present complaints which led to the diagnosis or prostatic carcinoma. Although our studies did not directly implicate diet as a risk factor, published reports strongly suggest diet as a critical factor in the development of prostatic carcinoma.

Age-related changes of arteries, veins, glands, and stroma in the prostate of black men from Washington, DC, and from Ibadan, Nigeria, and Accra, Ghana, West AFrica, were studied in a total of 795 consecutive, unselected prostate specimens removed at autopsy during a 7-year period (1973-1980). Except for age group 80 and over, aging changes in the prostate were more severe in all age groups in black men from Washington, DC, than in black men from Ibadan and Accra (P less than 0.01). However, when the intensity of age-dependent alterations was compared in either US or African black men with carcinoma and with no carcinoma, no significant differences were found. These findings do not support the idea that the aging process per se increases susceptibility to cancer.

Epidemiologic data reveal that the incidence rate of prostate gland carcinoma among the black population in the United States (US) is several times higher than among Nigerians. A collaborative study between the two countries was undertaken, and blood hormone (testosterone [T], dihydrotestosterone [DHT], estrone [E1], estradiol [E2], and prolactin [P1]), total acid phosphatase (TP), and prostatic acid phosphatase (PAP) profiles in the two population groups were compared. In the US groups (patients and controls) there were significantly higher levels of T (P less than 0.01) and E1 (P less than 0.05) compared with the Nigerians. Also, the US patients had significantly higher levels of T (P less than 0.05) and E1 (P less than 0.01) compared with their matched controls. In the Nigerians T but not E1 levels were significantly lower (P less than 0.05) in patients compared with controls. DHT, E2, and P1 were not significantly different in patients and controls between and within the populations. Nigerian patients had higher levels (P less than 0.001) of TP and PAP compared with US patients. It is concluded that differences in blood hormone profiles in the two population groups are based on factors other than the genetic makeup of the populations.